{"id":4806,"date":"2023-03-06T10:06:49","date_gmt":"2023-03-06T02:06:49","guid":{"rendered":"http:\/\/dh.oncolab.cn\/index.php\/2023\/03\/06\/monthly-updates-2023-02\/"},"modified":"2025-01-03T18:49:39","modified_gmt":"2025-01-03T10:49:39","slug":"monthly-updates-2023-02","status":"publish","type":"post","link":"http:\/\/dh.oncolab.cn\/index.php\/2023\/03\/06\/monthly-updates-2023-02\/","title":{"rendered":"Monthly Updates 2023.02"},"content":{"rendered":"
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01<\/strong><\/p>\n<\/section>\n<\/section>\n

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J Clin Invest. 20230223<\/strong><\/p>\n<\/section>\n<\/section>\n

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Glycolysis drives STING signaling to facilitate dendritic cell antitumor function<\/strong><\/p>\n

\u7cd6\u9175\u89e3\u901a\u8fc7\u9a71\u52a8STING\u4fe1\u53f7\u901a\u8def\u4fc3\u8fdb\u6811\u7a81\u72b6\u7ec6\u80de\u7684\u6297\u80bf\u7624\u529f\u80fd<\/strong><\/span><\/p>\n


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J Clin Invest. 2023 Feb 23;e166031. <\/em><\/p>\n

doi: <\/strong>10.1172\/JCI166031.<\/p>\n

PubMed: <\/strong>https:\/\/pubmed.ncbi.nlm.nih.gov\/36821379\/<\/span><\/p>\n


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Abstract<\/strong><\/span><\/p>\n

Activation of STING signaling in dendritic cells (DCs) promotes antitumor immunity. Aerobic glycolysis is a metabolic hallmark of activated DCs, but how the glycolytic pathway intersects with STING signaling in tumor-infiltrating DCs remains elusive. Here, we show that glycolysis drives STING signaling to facilitate DC-mediated antitumor immune responses. Tumor-infiltrating DCs exhibited elevated glycolysis, and blockade of glycolysis by DC-specific Ldha\/Ldhb double deletion resulted in defective antitumor immunity. Mechanistically, glycolysis augmented ATP production to boost STING activation and STING-dependent DC antitumor functions. Moreover, DC-intrinsic STING activation accelerated HIF-1a-mediated glycolysis and established a positive feedback loop. Importantly, glycolysis facilitated STING-dependent DC activity in tissue samples from non-small cell lung cancer patients. Our results provide mechanistic insight into how the crosstalk of glycolytic metabolism and STING signaling enhances DC antitumor activity and can be harnessed to improve cancer therapies.<\/p>\n


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\u6811\u7a81\u72b6\u7ec6\u80de(DCs)\u4e2dSTING\u4fe1\u53f7\u7684\u6fc0\u6d3b\u53ef\u4fc3\u8fdb\u6297\u80bf\u7624\u514d\u75ab\u3002\u6709\u6c27\u7cd6\u9175\u89e3\u662f\u6d3b\u5316DC\u7684\u4ee3\u8c22\u6807\u5fd7\uff0c\u4f46\u5728\u80bf\u7624\u6d78\u6da6\u6027DC\u4e2d\uff0c\u7cd6\u9175\u89e3\u9014\u5f84\u5982\u4f55\u4e0eSTING\u4fe1\u53f7\u4ea7\u751f\u4ea4\u4e92\u4ecd\u4e0d\u6e05\u695a\u3002\u5728\u672c\u7814\u7a76\u4e2d\uff0c\u6211\u4eec\u53d1\u73b0\u7cd6\u9175\u89e3\u901a\u8fc7\u9a71\u52a8STING\u4fe1\u53f7\u901a\u8def\u4fc3\u8fdb\u4e86DC\u4ecb\u5bfc\u7684\u6297\u80bf\u7624\u514d\u75ab\u5e94\u7b54\u3002\u80bf\u7624\u6d78\u6da6\u6027\u6811\u7a81\u72b6\u7ec6\u80de\u8868\u73b0\u51fa\u7cd6\u9175\u89e3\u6c34\u5e73\u7684\u5347\u9ad8\uff0c\u800c\u901a\u8fc7DC\u7279\u5f02\u6027\u7684Ldha\/Ldhb\u53cc\u6572\u9664\u6765\u963b\u65ad\u7cd6\u9175\u89e3\u4f1a\u5bfc\u81f4\u6297\u80bf\u7624\u514d\u75ab\u7684\u7f3a\u9677\u3002\u5728\u673a\u5236\u4e0a\uff0c\u7cd6\u9175\u89e3\u589e\u52a0ATP\u7684\u4ea7\u751f\uff0c\u4ece\u800c\u4fc3\u8fdb\u4e86STING\u7684\u6fc0\u6d3b\u548c\u4f9d\u8d56STING\u7684DC\u6297\u80bf\u7624\u529f\u80fd\u3002\u6b64\u5916\uff0cDC\u56fa\u6709\u7684STING\u6fc0\u6d3b\u52a0\u901f\u4e86HIF-1a\u4ecb\u5bfc\u7684\u7cd6\u9175\u89e3\u5e76\u5f62\u6210\u4e86\u6b63\u53cd\u9988\u73af\u8def\u3002\u91cd\u8981\u7684\u662f\uff0c\u7cd6\u9175\u89e3\u4fc3\u8fdb\u4e86\u975e\u5c0f\u7ec6\u80de\u80ba\u764c\u60a3\u8005\u7ec4\u7ec7\u6837\u672c\u4e2dSTING\u4f9d\u8d56\u7684DC\u6d3b\u6027\u3002\u6211\u4eec\u7684\u7814\u7a76\u7ed3\u679c\u63d0\u4f9b\u4e86\u5173\u4e8e\u7cd6\u9175\u89e3\u4ee3\u8c22\u548cSTING\u4fe1\u53f7\u5982\u4f55\u76f8\u4e92\u4f5c\u7528\u589e\u5f3aDC\u6297\u80bf\u7624\u6d3b\u6027\u7684\u673a\u5236\uff0c\u5e76\u6709\u671b\u7528\u4e8e\u6539\u5584\u764c\u75c7\u6cbb\u7597\u3002<\/p>\n


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Keywords: <\/strong><\/p>\n

Cancer immunotherapy; Glucose metabolism; Immunology; Innate immunity; Metabolism.<\/p>\n

\u764c\u75c7\u514d\u75ab\u6cbb\u7597\uff1b\u8461\u8404\u7cd6\u4ee3\u8c22\uff1b\u514d\u75ab\u5b66\uff1b\u5148\u5929\u514d\u75ab\uff1b\u4ee3\u8c22\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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02<\/strong><\/p>\n<\/section>\n<\/section>\n

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Mol Cancer. 20230216<\/strong><\/p>\n<\/section>\n<\/section>\n

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NK cells are never alone: crosstalk and communication in tumour microenvironments<\/strong><\/p>\n

NK\u7ec6\u80de\u4e0e\u80bf\u7624\u5fae\u73af\u5883\u95f4\u4ea4\u6d41\u548c\u76f8\u4e92\u4f5c\u7528<\/strong><\/span><\/p>\n


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Mol Cancer. 2023 Feb 16;22(1):34.<\/em><\/p>\n

doi:<\/strong> 10.1186\/s12943-023-01737-7.<\/p>\n

PubMed: <\/strong>https:\/\/pubmed.ncbi.nlm.nih.gov\/36797782\/<\/span><\/p>\n


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Abstract<\/strong><\/p>\n

Immune escape is a hallmark of cancer. The dynamic and heterogeneous tumour microenvironment (TME) causes insufficient infiltration and poor efficacy of natural killer (NK) cell-based immunotherapy, which becomes a key factor triggering tumour progression. Understanding the crosstalk between NK cells and the TME provides new insights for optimising NK cell-based immunotherapy. Here, we present new advances in direct or indirect crosstalk between NK cells and 9 specialised TMEs, including immune, metabolic, innervated niche, mechanical, and microbial microenvironments, summarise TME-mediated mechanisms of NK cell function inhibition, and highlight potential targeted therapies for NK-TME crosstalk. Importantly, we discuss novel strategies to overcome the inhibitory TME and provide an attractive outlook for the future.<\/p>\n


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\u514d\u75ab\u9003\u9038\u662f\u764c\u75c7\u7684\u6807\u5fd7\u3002\u52a8\u6001\u7684\u5f02\u8d28\u6027\u80bf\u7624\u5fae\u73af\u5883(TME)\u5bfc\u81f4\u81ea\u7136\u6740\u4f24(NK)\u7ec6\u80de\u514d\u75ab\u6cbb\u7597\u7684\u6d78\u6da6\u4e0d\u8db3\u548c\u7597\u6548\u4e0d\u4f73\uff0c\u8fd9\u6210\u4e3a\u89e6\u53d1\u80bf\u7624\u8fdb\u5c55\u7684\u5173\u952e\u56e0\u7d20\u3002\u4e86\u89e3NK\u7ec6\u80de\u548cTME\u4e4b\u95f4\u7684\u76f8\u4e92\u4f5c\u7528\u4e3a\u4f18\u5316\u57fa\u4e8eNK\u7ec6\u80de\u7684\u514d\u75ab\u6cbb\u7597\u63d0\u4f9b\u4e86\u65b0\u7684\u89c1\u89e3\u3002\u672c\u6587\u4ecb\u7ecd\u4e86NK\u7ec6\u80de\u4e0e\u514d\u75ab\u3001\u4ee3\u8c22\u548c\u5fae\u751f\u7269\u5fae\u73af\u5883\u7b499\u79cd\u7279\u5b9aTME\u4e4b\u95f4\u76f4\u63a5\u6216\u95f4\u63a5\u4ea4\u4e92\u4f5c\u7528\u7684\u65b0\u8fdb\u5c55\uff0c\u603b\u7ed3\u4e86TME\u4ecb\u5bfc\u7684NK\u7ec6\u80de\u529f\u80fd\u6291\u5236\u673a\u5236\uff0c\u5e76\u63d0\u51fa\u4e86\u9488\u5bf9NK\u7ec6\u80de\u4e0eTME\u4ea4\u4e92\u4f5c\u7528\u7684\u6f5c\u5728\u9776\u5411\u6cbb\u7597\u65b9\u6cd5\u3002\u91cd\u8981\u7684\u662f\uff0c\u6211\u4eec\u8ba8\u8bba\u4e86\u514b\u670d\u6291\u5236\u6027TME\u7684\u65b0\u7b56\u7565\uff0c\u5e76\u5bf9\u672a\u6765\u63d0\u51fa\u4e86\u5c55\u671b\u3002<\/p>\n


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Keywords:<\/strong><\/p>\n

Cancer; Communication; Crosstalk; NK cells; TME.<\/p>\n

\u764c\u75c7\uff1b\u4ea4\u6d41\uff1b\u4ea4\u4e92\uff1bNK\u7ec6\u80de\uff1b\u80bf\u7624\u5fae\u73af\u5883\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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03<\/strong><\/p>\n<\/section>\n<\/section>\n

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Nat Rev Cancer. 20230215<\/strong><\/p>\n<\/section>\n<\/section>\n

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A timeline of tumour-associated macrophage biology<\/strong><\/p>\n

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Nat Rev Cancer. 2023 Feb 15.<\/em><\/p>\n

doi: <\/strong>10.1038\/s41568-022-00547-1.<\/p>\n

PubMed: <\/strong>https:\/\/pubmed.ncbi.nlm.nih.gov\/36792751\/<\/span><\/p>\n


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Abstract<\/strong><\/p>\n

Tumour progression is modulated by the local microenvironment. This environment is populated by many immune cells, of which macrophages are among the most abundant. Clinical correlative data and a plethora of preclinical studies in mouse models of cancers have shown that tumour-associated macrophages (TAMs) play a cancer-promoting role. Within the primary tumour, TAMs promote tumour cell invasion and intravasation and tumour stem cell viability and induce angiogenesis. At the metastatic site, metastasis-associated macrophages promote extravasation, tumour cell survival and persistent growth, as well as maintain tumour cell dormancy in some contexts. In both the primary and metastatic sites, TAMs are suppressive to the activities of cytotoxic T and natural killer cells that have the potential to eradicate tumours. Such activities suggest that TAMs will be a major target for therapeutic intervention. In this Perspective article, we chronologically explore the evolution of our understanding of TAM biology put into the context of major enabling advances in macrophage biology.<\/p>\n


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\u80bf\u7624\u7684\u8fdb\u5c55\u53d7\u5c40\u90e8\u5fae\u73af\u5883\u7684\u8c03\u8282\u3002\u8fd9\u4e2a\u73af\u5883\u4e2d\u6709\u8bb8\u591a\u514d\u75ab\u7ec6\u80de\uff0c\u5176\u4e2d\u5de8\u566c\u7ec6\u80de\u662f\u6700\u4e30\u5bcc\u7684\u3002\u4e34\u5e8a\u76f8\u5173\u6570\u636e\u548c\u5927\u91cf\u5c0f\u9f20\u80bf\u7624\u6a21\u578b\u7684\u4e34\u5e8a\u524d\u7814\u7a76\u8868\u660e\uff0c\u80bf\u7624\u76f8\u5173\u5de8\u566c\u7ec6\u80de(TAMs)\u5177\u6709\u4fc3\u764c\u4f5c\u7528\u3002\u5728\u539f\u53d1\u80bf\u7624\u4e2d\uff0cTAMs\u4fc3\u8fdb\u80bf\u7624\u7ec6\u80de\u4fb5\u88ad\u548c\u5185\u6e17\uff0c\u4fc3\u8fdb\u80bf\u7624\u5e72\u7ec6\u80de\u6d3b\u6027\u5e76\u8bf1\u5bfc\u8840\u7ba1\u751f\u6210\u3002\u5728\u8f6c\u79fb\u90e8\u4f4d\uff0c\u4e0e\u8f6c\u79fb\u76f8\u5173\u7684\u5de8\u566c\u7ec6\u80de\u4fc3\u8fdb\u5916\u6e17\u3001\u80bf\u7624\u7ec6\u80de\u5b58\u6d3b\u548c\u6301\u7eed\u751f\u957f\uff0c\u5e76\u5728\u67d0\u4e9b\u60c5\u51b5\u4e0b\u7ef4\u6301\u80bf\u7624\u7ec6\u80de\u4f11\u7720\u3002\u5728\u539f\u53d1\u7076\u548c\u8f6c\u79fb\u7076\u4e2d\uff0cTAMs\u5747\u53ef\u6291\u5236\u7ec6\u80de\u6bd2\u6027T\u7ec6\u80de\u548c\u81ea\u7136\u6740\u4f24\u7ec6\u80de\u7684\u6d3b\u6027\uff0c\u800c\u8fd9\u4e9b\u7ec6\u80de\u5177\u6709\u6d88\u706d\u80bf\u7624\u7684\u6f5c\u529b\u3002\u8fd9\u4e9b\u8bc1\u636e\u63d0\u793aTAMs\u5c06\u6210\u4e3a\u6cbb\u7597\u5e72\u9884\u7684\u4e3b\u8981\u9776\u70b9\u3002\u5728\u8fd9\u7bc7\u6587\u7ae0\u4e2d\uff0c\u6211\u4eec\u5c06\u5de8\u566c\u7ec6\u80de\u751f\u7269\u5b66\u7684\u4e3b\u8981\u8fdb\u5c55\u6309\u65f6\u95f4\u987a\u5e8f\u8fdb\u884c\u5f52\u7eb3\u63a2\u8ba8\uff0c\u4ee5\u52a0\u6df1\u6211\u4eec\u5bf9TAM\u751f\u7269\u5b66\u7684\u7406\u89e3\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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04<\/strong><\/p>\n<\/section>\n<\/section>\n

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Mol Cancer. 20230210<\/strong><\/p>\n<\/section>\n<\/section>\n

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Roles of cancer-associated fibroblasts (CAFs) in anti- PD-1\/PD-L1 immunotherapy for solid cancers<\/strong><\/p>\n

\u80bf\u7624\u76f8\u5173\u6210\u7ea4\u7ef4\u7ec6\u80de(CAFs)\u5728\u6297PD-1\/PD-L1\u5b9e\u4f53\u764c\u514d\u75ab\u6cbb\u7597\u4e2d\u7684\u4f5c\u7528<\/strong><\/span><\/p>\n


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Mol Cancer. 2023 Feb 10;22(1):29.<\/em><\/p>\n

doi: <\/strong>10.1186\/s12943-023-01731-z.<\/p>\n

PubMed:<\/strong> <\/span>https:\/\/pubmed.ncbi.nlm.nih.gov\/36759842\/<\/span><\/p>\n


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Abstract<\/strong><\/p>\n

In recent years, breakthroughs have been made in tumor immunotherapy. However, tumor immunotherapy, particularly anti-PD-1\/PD-L1 immune checkpoint inhibitors, is effective in only a small percentage of patients in solid cancer. How to improve the efficiency of cancer immunotherapy is an urgent problem to be solved. As we all know, the state of the tumor microenvironment (TME) is an essential factor affecting the effectiveness of tumor immunotherapy, and the cancer-associated fibroblasts (CAFs) in TME have attracted much attention in recent years. As one of the main components of TME, CAFs interact with cancer cells and immune cells by secreting cytokines and vesicles, participating in ECM remodeling, and finally affecting the immune response process. With the in-depth study of CAFs heterogeneity, new strategies are provided for finding targets of combination immunotherapy and predicting immune efficacy. In this review, we focus on the role of CAFs in the solid cancer immune microenvironment, and then further elaborate on the potential mechanisms and pathways of CAFs influencing anti-PD-1\/PD-L1 immunotherapy. In addition, we summarize the potential clinical application value of CAFs-related targets and markers in solid cancers.<\/p>\n


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\u8fd1\u5e74\u6765\uff0c\u80bf\u7624\u514d\u75ab\u6cbb\u7597\u53d6\u5f97\u4e86\u7a81\u7834\u6027\u8fdb\u5c55\u3002\u7136\u800c\uff0c\u80bf\u7624\u514d\u75ab\u7597\u6cd5\uff0c\u5c24\u5176\u662f\u6297PD-1\/PD-L1\u514d\u75ab\u68c0\u67e5\u70b9\u6291\u5236\u5242\uff0c\u4ec5\u5bf9\u4e00\u5c0f\u90e8\u5206\u5b9e\u4f53\u764c\u60a3\u8005\u6709\u6548\u3002\u5982\u4f55\u63d0\u9ad8\u80bf\u7624\u514d\u75ab\u6cbb\u7597\u7684\u6548\u7387\u662f\u4e00\u4e2a\u4e9f\u5f85\u89e3\u51b3\u7684\u95ee\u9898\u3002\u4f17\u6240\u5468\u77e5\uff0c\u80bf\u7624\u5fae\u73af\u5883(tumor microenvironment, TME)\u72b6\u6001\u662f\u5f71\u54cd\u80bf\u7624\u514d\u75ab\u6cbb\u7597\u6709\u6548\u6027\u7684\u91cd\u8981\u56e0\u7d20\uff0c\u5176\u4e2d\u80bf\u7624\u76f8\u5173\u6210\u7ea4\u7ef4\u7ec6\u80de(cancer-associated fibroblasts, CAFs)\u8fd1\u5e74\u6765\u5907\u53d7\u5173\u6ce8\u3002CAFs\u4f5c\u4e3aTME\u7684\u4e3b\u8981\u6210\u5206\u4e4b\u4e00\uff0c\u901a\u8fc7\u5206\u6ccc\u7ec6\u80de\u56e0\u5b50\u548c\u56ca\u6ce1\u4e0e\u764c\u7ec6\u80de\u4ee5\u53ca\u514d\u75ab\u7ec6\u80de\u76f8\u4e92\u4f5c\u7528\uff0c\u53c2\u4e0eECM\u91cd\u5851\uff0c\u6700\u7ec8\u5f71\u54cd\u514d\u75ab\u5e94\u7b54\u8fc7\u7a0b\u3002\u968f\u7740\u5bf9CAFs\u5f02\u8d28\u6027\u7814\u7a76\u7684\u6df1\u5165\uff0c\u4e3a\u5bfb\u627e\u8054\u5408\u514d\u75ab\u6cbb\u7597\u9776\u70b9\u548c\u9884\u6d4b\u514d\u75ab\u7597\u6548\u63d0\u4f9b\u4e86\u65b0\u7684\u7b56\u7565\u3002\u672c\u6587\u5c06\u56f4\u7ed5CAFs\u5728\u5b9e\u4f53\u80bf\u7624\u514d\u75ab\u5fae\u73af\u5883\u4e2d\u7684\u4f5c\u7528\uff0c\u8fdb\u4e00\u6b65\u9610\u8ff0CAFs\u5f71\u54cd\u6297PD-1\/PD-L1\u514d\u75ab\u6cbb\u7597\u7684\u6f5c\u5728\u673a\u5236\u548c\u901a\u8def\u3002\u6b64\u5916\uff0c\u672c\u6587\u8fd8\u603b\u7ed3\u4e86CAFs\u76f8\u5173\u9776\u70b9\u548c\u6807\u5fd7\u7269\u5728\u5b9e\u4f53\u764c\u4e2d\u7684\u6f5c\u5728\u4e34\u5e8a\u5e94\u7528\u4ef7\u503c\u3002<\/p>\n

Keywords:<\/strong><\/p>\n

Cancer-associated fibroblasts; Immunotherapy; PD-1\/PD-L1 inhibitors.<\/p>\n

\u80bf\u7624\u76f8\u5173\u6210\u7ea4\u7ef4\u7ec6\u80de\uff1b\u514d\u75ab\u6cbb\u7597\uff1bPD-1\/PD-L1\u6291\u5236\u5242\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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05<\/strong><\/p>\n<\/section>\n<\/section>\n

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Cancer Cell. 20230209<\/strong><\/p>\n<\/section>\n<\/section>\n

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\u2726<\/p>\n<\/section>\n<\/section>\n

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Metabolic programming and immune suppression in the tumor microenvironment<\/strong><\/p>\n

\u80bf\u7624\u5fae\u73af\u5883\u4e2d\u7684\u4ee3\u8c22\u7f16\u7a0b\u548c\u514d\u75ab\u6291\u5236<\/strong><\/span><\/p>\n


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Cancer Cell. 2023 Feb 9;S1535-6108(23)00009-0.<\/em><\/p>\n

doi:<\/strong> 10.1016\/j.ccell.2023.01.009.<\/p>\n

PubMed:<\/strong> <\/span>https:\/\/pubmed.ncbi.nlm.nih.gov\/36801000\/<\/span><\/p>\n


<\/p>\n

Abstract<\/strong><\/p>\n

Increased glucose metabolism and uptake are characteristic of many tumors and used clinically to diagnose and monitor cancer progression. In addition to cancer cells, the tumor microenvironment (TME) encompasses a wide range of stromal, innate, and adaptive immune cells. Cooperation and competition between these cell populations supports tumor proliferation, progression, metastasis, and immune evasion. Cellular heterogeneity leads to metabolic heterogeneity because metabolic programs within the tumor are dependent not only on the TME cellular composition but also on cell states, location, and nutrient availability. In addition to driving metabolic plasticity of cancer cells, altered nutrients and signals in the TME can lead to metabolic immune suppression of effector cells and promote regulatory immune cells. Here we discuss how metabolic programming of cells within the TME promotes tumor proliferation, progression, and metastasis. We also discuss how targeting metabolic heterogeneity may offer therapeutic opportunities to overcome immune suppression and augment immunotherapies.<\/p>\n


<\/p>\n

\u8461\u8404\u7cd6\u4ee3\u8c22\u548c\u6444\u53d6\u589e\u52a0\u662f\u8bb8\u591a\u80bf\u7624\u7684\u7279\u5f81\uff0c\u4e34\u5e8a\u4e0a\u7528\u4e8e\u8bca\u65ad\u548c\u76d1\u6d4b\u764c\u75c7\u8fdb\u5c55\u3002\u9664\u764c\u7ec6\u80de\u5916\uff0c\u80bf\u7624\u5fae\u73af\u5883(tumor microenvironment, TME)\u8fd8\u5305\u62ec\u5e7f\u6cdb\u7684\u57fa\u8d28\u3001\u56fa\u6709\u548c\u9002\u5e94\u6027\u514d\u75ab\u7ec6\u80de\u3002\u8fd9\u4e9b\u7ec6\u80de\u7fa4\u4e4b\u95f4\u7684\u5408\u4f5c\u548c\u7ade\u4e89\u652f\u6301\u80bf\u7624\u7684\u589e\u6b96\u3001\u8fdb\u5c55\u3001\u8f6c\u79fb\u548c\u514d\u75ab\u9003\u9038\u3002\u7ec6\u80de\u5f02\u8d28\u6027\u5bfc\u81f4\u4ee3\u8c22\u5f02\u8d28\u6027\uff0c\u56e0\u4e3a\u80bf\u7624\u5185\u7684\u4ee3\u8c22\u7a0b\u5e8f\u4e0d\u4ec5\u53d6\u51b3\u4e8eTME\u7ec6\u80de\u7684\u7ec4\u6210\uff0c\u8fd8\u53d6\u51b3\u4e8e\u7ec6\u80de\u7684\u72b6\u6001\u3001\u4f4d\u7f6e\u548c\u517b\u5206\u7684\u53ef\u5229\u7528\u6027\u3002\u9664\u4e86\u9a71\u52a8\u764c\u7ec6\u80de\u7684\u4ee3\u8c22\u53ef\u5851\u6027\uff0cTME\u4e2d\u8425\u517b\u7269\u8d28\u548c\u4fe1\u53f7\u7684\u6539\u53d8\u53ef\u5bfc\u81f4\u6548\u5e94\u7ec6\u80de\u7684\u4ee3\u8c22\u6027\u514d\u75ab\u6291\u5236\uff0c\u4fc3\u8fdb\u8c03\u8282\u6027\u514d\u75ab\u7ec6\u80de\u3002\u672c\u6587\u5c06\u8ba8\u8bbaTME\u4e2d\u7ec6\u80de\u7684\u4ee3\u8c22\u7f16\u7a0b\u5982\u4f55\u4fc3\u8fdb\u80bf\u7624\u7684\u589e\u6b96\u3001\u8fdb\u5c55\u548c\u8f6c\u79fb\u3002\u6211\u4eec\u8fd8\u8ba8\u8bba\u4e86\u9776\u5411\u4ee3\u8c22\u5f02\u8d28\u6027\u5982\u4f55\u4e3a\u514b\u670d\u514d\u75ab\u6291\u5236\u548c\u589e\u5f3a\u514d\u75ab\u6cbb\u7597\u63d0\u4f9b\u6cbb\u7597\u673a\u4f1a\u3002<\/p>\n


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Keywords:<\/strong><\/p>\n

immune; metabolism; metastasis; plasticity; tumor microenvironment.<\/p>\n

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06<\/strong><\/p>\n<\/section>\n<\/section>\n

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Cancer Cell. 20230209<\/strong><\/p>\n<\/section>\n<\/section>\n

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Dissecting the immune suppressive human prostate tumor microenvironment via integrated single-cell and spatial transcriptomic analyses<\/strong><\/p>\n

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Nat Commun. 2023 Feb 7;14(1):663.<\/em><\/p>\n

doi:<\/strong> 10.1038\/s41467-023-36325-2.<\/p>\n

PubMed:<\/strong> <\/span>https:\/\/pubmed.ncbi.nlm.nih.gov\/36750562\/<\/span><\/p>\n


<\/p>\n

Abstract<\/strong><\/p>\n

The treatment of low-risk primary prostate cancer entails active surveillance only, while high-risk disease requires multimodal treatment including surgery, radiation therapy, and hormonal therapy. Recurrence and development of metastatic disease remains a clinical problem, without a clear understanding of what drives immune escape and tumor progression. Here, we comprehensively describe the tumor microenvironment of localized prostate cancer in comparison with adjacent normal samples and healthy controls. Single-cell RNA sequencing and high-resolution spatial transcriptomic analyses reveal tumor context dependent changes in gene expression. Our data indicate that an immune suppressive tumor microenvironment associates with suppressive myeloid populations and exhausted T-cells, in addition to high stromal angiogenic activity. We infer cell-to-cell relationships from high throughput ligand-receptor interaction measurements within undissociated tissue sections. Our work thus provides a highly detailed and comprehensive resource of the prostate tumor microenvironment as well as tumor-stromal cell interactions.<\/p>\n


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07<\/strong><\/p>\n<\/section>\n<\/section>\n

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Cancer Discov. 20230206<\/strong><\/p>\n<\/section>\n<\/section>\n

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Discovery of Targets for Immune-Metabolic Antitumor Drugs Identifies Estrogen-Related Receptor Alpha<\/strong><\/p>\n

\u514d\u75ab\u4ee3\u8c22\u6297\u80bf\u7624\u836f\u7269\u9776\u70b9\u7684\u53d1\u73b0-\u4ee5\u96cc\u6fc0\u7d20\u76f8\u5173\u53d7\u4f53\u03b1\u4e3a\u4f8b<\/strong><\/span><\/p>\n


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Cancer Discov. 2023 Feb 6;OF1-OF30.<\/em><\/p>\n

doi: <\/strong>10.1158\/2159-8290.CD-22-0244.<\/p>\n

PubMed:<\/strong> <\/span>https:\/\/pubmed.ncbi.nlm.<\/span>nih.gov\/36745048\/<\/span><\/p>\n


<\/p>\n

Abstract<\/strong><\/p>\n

Drugs that kill tumors through multiple mechanisms have the potential for broad clinical benefits. Here, we first developed an in silico multiomics approach (BipotentR) to find cancer cell-specific regulators that simultaneously modulate tumor immunity and another oncogenic pathway and then used it to identify 38 candidate immune-metabolic regulators. We show the tumor activities of these regulators stratify patients with melanoma by their response to anti-PD-1 using machine learning and deep neural approaches, which improve the predictive power of current biomarkers. The topmost identified regulator, ESRRA, is activated in immunotherapy-resistant tumors. Its inhibition killed tumors by suppressing energy metabolism and activating two immune mechanisms: (i) cytokine induction, causing proinflammatory macrophage polarization, and (ii) antigen-presentation stimulation, recruiting CD8+ T cells into tumors. We also demonstrate a wide utility of BipotentR by applying it to angiogenesis and growth suppressor evasion pathways. BipotentR (http:\/\/bipotentr.dfci.harvard.edu\/) provides a resource for evaluating patient response and discovering drug targets that act simultaneously through multiple mechanisms.<\/p>\n


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08<\/strong><\/p>\n<\/section>\n<\/section>\n

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Mol Cancer. 20230204<\/strong><\/p>\n<\/section>\n<\/section>\n

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Regulatory cells and the effect of cancer immunotherapy<\/strong><\/p>\n

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Mol Cancer. 2023 Feb 4;22(1):26.<\/em><\/p>\n

doi: <\/strong>10.1186\/s12943-023-01714-0.<\/p>\n

PubMed:<\/strong> <\/span>https:\/\/pubmed.ncbi.nlm.nih.gov\/36739406\/<\/span><\/p>\n


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Abstract<\/p>\n

Several mechanisms and cell types are involved in the regulation of the immune response. These include mostly regulatory T cells (Tregs), regulatory macrophages (Mregs), myeloid suppressor cells (MDSCs) and other regulatory cell types such as tolerogenic dendritic cells (tolDCs), regulatory B cells (Bregs), and mesenchymal stem cells (MSCs). These regulatory cells, known for their ability to suppress immune responses, can also suppress the anti-tumor immune response. The infiltration of many regulatory cells into tumor tissues is therefore associated with a poor prognosis. There is growing evidence that elimination of Tregs enhances anti-tumor immune responses. However, the systemic depletion of Treg cells can simultaneously cause deleterious autoimmunity. Furthermore, since regulatory cells are characterized by their high level of expression of immune checkpoints, it is also expected that immune checkpoint inhibitors perform part of their function by blocking these molecules and enhancing the immune response. This indicates that immunotherapy does not only act by activating specific effector T cells but can also directly or indirectly attenuate the suppressive activity of regulatory cells in tumor tissues. This review aims to draw together our current knowledge about the effect of immunotherapy on the various types of regulatory cells, and how these effects may be beneficial in the response to immunotherapy.<\/p>\n


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\u591a\u79cd\u673a\u5236\u548c\u7ec6\u80de\u7c7b\u578b\u53c2\u4e0e\u514d\u75ab\u5e94\u7b54\u7684\u8c03\u8282\u3002\u8fd9\u4e9b\u7ec6\u80de\u4e3b\u8981\u5305\u62ec\u8c03\u8282\u6027T\u7ec6\u80de(Tregs)\u3001\u8c03\u8282\u6027\u5de8\u566c\u7ec6\u80de(Mregs)\u3001\u9ad3\u6837\u6291\u5236\u7ec6\u80de(MDSCs)\u548c\u5176\u4ed6\u8c03\u8282\u6027\u7ec6\u80de\u7c7b\u578b\uff0c\u5982\u8010\u53d7\u6027\u6811\u7a81\u72b6\u7ec6\u80de(tolDCs)\u3001\u8c03\u8282\u6027B\u7ec6\u80de(Bregs)\u548c\u95f4\u5145\u8d28\u5e72\u7ec6\u80de(MSCs)\u3002\u8fd9\u4e9b\u8c03\u8282\u7ec6\u80de\uff0c\u4ee5\u5176\u6291\u5236\u514d\u75ab\u53cd\u5e94\u7684\u80fd\u529b\u800c\u95fb\u540d\uff0c\u4e5f\u53ef\u4ee5\u6291\u5236\u6297\u80bf\u7624\u514d\u75ab\u53cd\u5e94\u3002\u56e0\u6b64\uff0c\u8bb8\u591a\u8c03\u8282\u6027\u7ec6\u80de\u5728\u80bf\u7624\u7ec4\u7ec7\u4e2d\u7684\u6d78\u6da6\u4e0e\u4e0d\u826f\u9884\u540e\u76f8\u5173\u3002\u8d8a\u6765\u8d8a\u591a\u7684\u8bc1\u636e\u8868\u660e\uff0c\u6e05\u9664Tregs\u53ef\u589e\u5f3a\u6297\u80bf\u7624\u514d\u75ab\u5e94\u7b54\u3002\u7136\u800c\uff0c\u5168\u8eab\u6027\u6e05\u9664Treg\u7ec6\u80de\u53ef\u540c\u65f6\u5f15\u8d77\u6709\u5bb3\u7684\u81ea\u8eab\u514d\u75ab\u3002\u6b64\u5916\uff0c\u7531\u4e8e\u8c03\u8282\u6027\u7ec6\u80de\u7684\u7279\u70b9\u662f\u5176\u9ad8\u6c34\u5e73\u8868\u8fbe\u514d\u75ab\u68c0\u67e5\u70b9\uff0c\u56e0\u6b64\u9884\u671f\u514d\u75ab\u68c0\u67e5\u70b9\u6291\u5236\u5242\u4e5f\u53ef\u4ee5\u901a\u8fc7\u963b\u65ad\u8fd9\u4e9b\u5206\u5b50\u548c\u589e\u5f3a\u514d\u75ab\u53cd\u5e94\u6765\u53d1\u6325\u90e8\u5206\u529f\u80fd\u3002\u8fd9\u8868\u660e\u514d\u75ab\u6cbb\u7597\u4e0d\u4ec5\u901a\u8fc7\u6fc0\u6d3b\u7279\u5f02\u6027\u6548\u5e94T\u7ec6\u80de\u53d1\u6325\u4f5c\u7528\uff0c\u800c\u4e14\u53ef\u4ee5\u76f4\u63a5\u6216\u95f4\u63a5\u51cf\u5f31\u80bf\u7624\u7ec4\u7ec7\u4e2d\u8c03\u8282\u6027T\u7ec6\u80de\u7684\u6291\u5236\u6d3b\u6027\u3002\u8fd9\u7bc7\u7efc\u8ff0\u65e8\u5728\u603b\u7ed3\u6211\u4eec\u76ee\u524d\u5173\u4e8e\u514d\u75ab\u6cbb\u7597\u5bf9\u5404\u79cd\u7c7b\u578b\u8c03\u8282\u6027\u7ec6\u80de\u7684\u5f71\u54cd\u7684\u77e5\u8bc6\uff0c\u4ee5\u53ca\u5982\u4f55\u4f7f\u8fd9\u4e9b\u5f71\u54cd\u6709\u5229\u4e8e\u5bf9\u514d\u75ab\u6cbb\u7597\u7684\u5e94\u7b54\u3002<\/p>\n


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Keywords:<\/strong><\/p>\n

Checkpoint inhibitors; Immunotherapy; MDSCs; Regulatory cells; TAMs; Tregs; Tumor.<\/p>\n

\u68c0\u67e5\u70b9\u6291\u5236\u5242\uff1b\u514d\u75ab\u6cbb\u7597\uff1b\u9ad3\u6e90\u6027\u6291\u5236\u7ec6\u80de\uff1b\u8c03\u8282\u7ec6\u80de\uff1b\u80bf\u7624\u76f8\u5173\u5de8\u566c\u7ec6\u80de\uff1b\u4e9a\u7fa4\uff1b\u80bf\u7624\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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09<\/strong><\/p>\n<\/section>\n<\/section>\n

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Nat Commun. 20230202<\/strong><\/p>\n<\/section>\n<\/section>\n

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Estimation of cell lineages in tumors from spatial transcriptomics data<\/strong><\/p>\n

\u4ece\u7a7a\u95f4\u8f6c\u5f55\u7ec4\u5b66\u6570\u636e\u63a8\u65ad\u80bf\u7624\u4e2d\u7684\u7ec6\u80de\u8c31\u7cfb<\/strong><\/span><\/p>\n


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Nat Commun. 2023 Feb 2;14(1):568.<\/em><\/p>\n

doi: <\/strong>10.1038\/s41467-023-36062-6.<\/p>\n

PubMed:<\/strong> <\/span>https:\/\/pubmed.ncbi.nlm.nih.gov\/36732531\/<\/span><\/p>\n


<\/p>\n

Abstract<\/strong><\/p>\n

Spatial transcriptomics (ST) technology through in situ capturing has enabled topographical gene expression profiling of tumor tissues. However, each capturing spot may contain diverse immune and malignant cells, with different cell densities across tissue regions. Cell type deconvolution in tumor ST data remains challenging for existing methods designed to decompose general ST or bulk tumor data. We develop the Spatial Cellular Estimator for Tumors (SpaCET) to infer cell identities from tumor ST data. SpaCET first estimates cancer cell abundance by integrating a gene pattern dictionary of copy number alterations and expression changes in common malignancies. A constrained regression model then calibrates local cell densities and determines immune and stromal cell lineage fractions. SpaCET provides higher accuracy than existing methods based on simulation and real ST data with matched double-blind histopathology annotations as ground truth. Further, coupling cell fractions with ligand-receptor coexpression analysis, SpaCET reveals how intercellular interactions at the tumor-immune interface promote cancer progression.<\/p>\n


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\u7a7a\u95f4\u8f6c\u5f55\u7ec4\u5b66(ST)\u6280\u672f\u901a\u8fc7\u539f\u4f4d\u6355\u83b7\u5b9e\u73b0\u4e86\u80bf\u7624\u7ec4\u7ec7\u7684\u57fa\u56e0\u8868\u8fbe\u8c31\u5206\u6790\u3002\u7136\u800c\uff0c\u6bcf\u4e2a\u6355\u83b7\u70b9\u53ef\u80fd\u5305\u542b\u4e0d\u540c\u7684\u514d\u75ab\u548c\u6076\u6027\u7ec6\u80de\uff0c\u4e0d\u540c\u7ec4\u7ec7\u533a\u57df\u7684\u7ec6\u80de\u5bc6\u5ea6\u4e0d\u540c\u3002\u5bf9\u4e8e\u73b0\u6709\u7684\u7528\u4e8e\u5206\u89e3\u4e00\u822cST\u6216bulk\u80bf\u7624\u6570\u636e\u7684\u65b9\u6cd5\u6765\u8bf4\uff0c\u80bf\u7624ST\u6570\u636e\u4e2d\u7684\u7ec6\u80de\u7c7b\u578b\u53cd\u5377\u79ef\u4ecd\u7136\u5177\u6709\u6311\u6218\u6027\u3002\u6211\u4eec\u5f00\u53d1\u4e86\u80bf\u7624\u7a7a\u95f4\u7ec6\u80de\u63a8\u65ad\u5668(SpaCET)\u6765\u4ece\u80bf\u7624ST\u6570\u636e\u4e2d\u63a8\u65ad\u7ec6\u80de\u7c7b\u578b\u3002SpaCET\u9996\u5148\u901a\u8fc7\u6574\u5408\u5e38\u89c1\u6076\u6027\u80bf\u7624\u4e2d\u62f7\u8d1d\u6570\u6539\u53d8\u548c\u8868\u8fbe\u53d8\u5316\u7684\u57fa\u56e0\u6a21\u5f0f\u6765\u8bc4\u4f30\u764c\u7ec6\u80de\u4e30\u5ea6\u3002\u7136\u540e\uff0c\u901a\u8fc7\u4e00\u4e2a\u7ea6\u675f\u56de\u5f52\u6a21\u578b\u6821\u51c6\u5c40\u90e8\u7ec6\u80de\u5bc6\u5ea6\uff0c\u5e76\u786e\u5b9a\u514d\u75ab\u7ec6\u80de\u548c\u57fa\u8d28\u7ec6\u80de\u7684\u8c31\u7cfb\u7ec4\u5206\u3002\u4e0e\u73b0\u6709\u7684\u57fa\u4e8e\u6a21\u62df\u548c\u771f\u5b9eST\u6570\u636e\u3001\u5339\u914d\u7684\u53cc\u76f2\u7ec4\u7ec7\u75c5\u7406\u5b66\u6ce8\u91ca\u7684\u65b9\u6cd5\u76f8\u6bd4\uff0cSpaCET\u5177\u6709\u66f4\u9ad8\u7684\u51c6\u786e\u6027\u3002\u6b64\u5916\uff0c\u901a\u8fc7\u5c06\u7ec6\u80de\u7ec4\u5206\u4e0e\u914d\u4f53-\u53d7\u4f53\u5171\u8868\u8fbe\u5206\u6790\u8026\u8054\uff0cSpaCET\u63ed\u793a\u4e86\u80bf\u7624-\u514d\u75ab\u7684\u7ec6\u80de\u95f4\u76f8\u4e92\u4f5c\u7528\u662f\u5982\u4f55\u4fc3\u8fdb\u764c\u75c7\u8fdb\u5c55\u7684\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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10<\/strong><\/p>\n<\/section>\n<\/section>\n

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Nature. 20230201-1<\/strong><\/p>\n<\/section>\n<\/section>\n

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Single-cell spatial immune landscapes of primary and metastatic brain tumours<\/strong><\/p>\n

\u539f\u53d1\u6027\u548c\u8f6c\u79fb\u6027\u8111\u80bf\u7624\u7684\u5355\u7ec6\u80de\u7a7a\u95f4\u514d\u75ab\u666f\u89c2<\/strong><\/span><\/p>\n


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Nature. 2023 Feb 1.<\/em><\/p>\n

doi:<\/strong> 10.1038\/s41586-022-05680-3. <\/p>\n

PubMed:<\/strong> <\/span>https:\/\/pubmed.ncbi.nlm.nih.gov\/36725935\/<\/span><\/p>\n


<\/p>\n

Abstract<\/strong><\/p>\n

Single-cell technologies have enabled the characterization of the tumour microenvironment at unprecedented depth and have revealed vast cellular diversity among tumour cells and their niche. Anti-tumour immunity relies on cell-cell relationships within the tumour microenvironment1,2, yet many single-cell studies lack spatial context and rely on dissociated tissues3. Here we applied imaging mass cytometry to characterize the immunological landscape of 139 high-grade glioma and 46 brain metastasis tumours from patients. Single-cell analysis of more than 1.1 million cells across 389 high-dimensional histopathology images enabled the spatial resolution of immune lineages and activation states, revealing differences in immune landscapes between primary tumours and brain metastases from diverse solid cancers. These analyses revealed cellular neighbourhoods associated with survival in patients with glioblastoma, which we leveraged to identify a unique population of myeloperoxidase (MPO)-positive macrophages associated with long-term survival. Our findings provide insight into the biology of primary and metastatic brain tumours, reinforcing the value of integrating spatial resolution to single-cell datasets to dissect the microenvironmental contexture of cancer.<\/p>\n


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\u5355\u7ec6\u80de\u6280\u672f\u4f7f\u80bf\u7624\u5fae\u73af\u5883\u7684\u8868\u5f81\u8fbe\u5230\u4e86\u524d\u6240\u672a\u6709\u7684\u6df1\u5ea6\uff0c\u5e76\u63ed\u793a\u4e86\u80bf\u7624\u7ec6\u80de\u53ca\u5176\u5468\u56f4\u73af\u5883\u7684\u5de8\u5927\u7ec6\u80de\u591a\u6837\u6027\u3002\u6297\u80bf\u7624\u514d\u75ab\u4f9d\u8d56\u4e8e\u80bf\u7624\u5fae\u73af\u5883\u4e2d\u7684\u7ec6\u80de-\u7ec6\u80de\u95f4\u5173\u7cfb\uff0c\u4f46\u8bb8\u591a\u5355\u7ec6\u80de\u7814\u7a76\u7f3a\u4e4f\u7a7a\u95f4\u80cc\u666f\uff0c\u800c\u4f9d\u8d56\u4e8e\u5206\u79bb\u7684\u7ec4\u7ec7\u3002\u5728\u8fd9\u91cc\uff0c\u6211\u4eec\u5e94\u7528\u6210\u50cf\u8d28\u8c31\u7ec6\u80de\u672f\u6765\u8868\u5f81139\u4f8b\u9ad8\u7ea7\u522b\u80f6\u8d28\u7624\u548c46\u4f8b\u8111\u8f6c\u79fb\u7624\u60a3\u8005\u7684\u514d\u75ab\u7279\u5f81\u3002\u5bf9389\u5f20\u9ad8\u7ef4\u7ec4\u7ec7\u75c5\u7406\u5b66\u56fe\u50cf\u4e2d\u7684\u8d85\u8fc7110\u4e07\u4e2a\u7ec6\u80de\u8fdb\u884c\u7684\u5355\u7ec6\u80de\u5206\u6790\u4f7f\u514d\u75ab\u8c31\u7cfb\u548c\u6fc0\u6d3b\u72b6\u6001\u7684\u7a7a\u95f4\u5206\u8fa8\u7387\u6210\u4e3a\u53ef\u80fd\uff0c\u63ed\u793a\u4e86\u4e0d\u540c\u5b9e\u4f53\u764c\u539f\u53d1\u80bf\u7624\u548c\u8111\u8f6c\u79fb\u7624\u4e4b\u95f4\u7684\u514d\u75ab\u666f\u89c2\u5dee\u5f02\u3002\u8fd9\u4e9b\u5206\u6790\u63ed\u793a\u4e86\u4e0e\u80f6\u8d28\u6bcd\u7ec6\u80de\u7624\u60a3\u8005\u751f\u5b58\u76f8\u5173\u7684\u7ec6\u80de\u76f8\u90bb\u5173\u7cfb\uff0c\u6211\u4eec\u5229\u7528\u8fd9\u4e00\u5206\u6790\u786e\u5b9a\u4e86\u4e0e\u957f\u671f\u751f\u5b58\u76f8\u5173\u7684\u9ad3\u8fc7\u6c27\u5316\u7269\u9176(MPO)\u9633\u6027\u5de8\u566c\u7ec6\u80de\u7fa4\u4f53\u3002\u6211\u4eec\u7684\u53d1\u73b0\u4e3a\u539f\u53d1\u6027\u548c\u8f6c\u79fb\u6027\u8111\u80bf\u7624\u7684\u751f\u7269\u5b66\u63d0\u4f9b\u4e86\u89c1\u89e3\uff0c\u5f3a\u5316\u4e86\u5c06\u7a7a\u95f4\u5206\u8fa8\u7387\u6574\u5408\u5230\u5355\u7ec6\u80de\u6570\u636e\u96c6\u4ee5\u89e3\u6790\u764c\u75c7\u5fae\u73af\u5883\u80cc\u666f\u7684\u4ef7\u503c\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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11<\/strong><\/p>\n<\/section>\n<\/section>\n

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Nature. 20230201-1<\/strong><\/p>\n<\/section>\n<\/section>\n

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Single-cell spatial landscapes of the lung tumour immune microenvironment<\/strong><\/p>\n

\u80ba\u764c\u514d\u75ab\u5fae\u73af\u5883\u7684\u5355\u7ec6\u80de\u7a7a\u95f4\u666f\u89c2<\/strong><\/span><\/p>\n


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Nature. 2023 Feb 1.<\/em><\/p>\n

doi:<\/strong> 10.1038\/s41586-022-05672-3.<\/p>\n

PubMed:<\/strong> <\/span>https:\/\/pubmed.ncbi.nlm.nih.gov\/36725934\/<\/span><\/p>\n


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Abstract<\/strong><\/p>\n

Single-cell technologies have revealed the complexity of the tumour immune microenvironment with unparalleled resolution. Most clinical strategies rely on histopathological stratification of tumour subtypes, yet the spatial context of single-cell phenotypes within these stratified subgroups is poorly understood. Here we apply imaging mass cytometry to characterize the tumour and immunological landscape of samples from 416 patients with lung adenocarcinoma across five histological patterns. We resolve more than 1.6 million cells, enabling spatial analysis of immune lineages and activation states with distinct clinical correlates, including survival. Using deep learning, we can predict with high accuracy those patients who will progress after surgery using a single 1-mm2 tumour core, which could be informative for clinical management following surgical resection. Our dataset represents a valuable resource for the non-small cell lung cancer research community and exemplifies the utility of spatial resolution within single-cell analyses. This study also highlights how artificial intelligence can improve our understanding of microenvironmental features that underlie cancer progression and may influence future clinical practice.<\/p>\n


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12<\/strong><\/p>\n<\/section>\n<\/section>\n

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J Clin Invest. 20230201-1<\/strong><\/p>\n<\/section>\n<\/section>\n

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PD-L1 translocation to the plasma membrane enables tumor immune evasion through MIB2 ubiquitination<\/strong><\/p>\n

PD-L1\u8f6c\u4f4d\u81f3\u8d28\u819c\u53ef\u901a\u8fc7MIB2\u6cdb\u7d20\u5316\u5b9e\u73b0\u80bf\u7624\u514d\u75ab\u9003\u9038<\/strong><\/span><\/p>\n


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J Clin Invest. 2023 Feb 1;133(3):e160456.<\/em><\/p>\n

doi: <\/strong>10.1172\/JCI160456.<\/p>\n

PubMed:<\/strong> <\/span>https:\/\/pubmed.ncbi.nlm.nih.gov\/36719382\/<\/span><\/p>\n


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Abstract<\/p>\n

Programmed death-ligand 1 (PD-L1), a critical immune checkpoint ligand, is a transmembrane protein synthesized in the endoplasmic reticulum of tumor cells and transported to the plasma membrane to interact with programmed death 1 (PD-1) expressed on T cell surface. This interaction delivers coinhibitory signals to T cells, thereby suppressing their function and allowing evasion of antitumor immunity. Most companion or complementary diagnostic devices for assessing PD-L1 expression levels in tumor cells used in the clinic or in clinical trials require membranous staining. However, the mechanism driving PD-L1 translocation to the plasma membrane after de novo synthesis is poorly understood. Herein, we showed that mind bomb homolog 2 (MIB2) is required for PD-L1 transportation from the trans-Golgi network (TGN) to the plasma membrane of cancer cells. MIB2 deficiency led to fewer PD-L1 proteins on the tumor cell surface and promoted antitumor immunity in mice. Mechanistically, MIB2 catalyzed nonproteolytic K63-linked ubiquitination of PD-L1, facilitating PD-L1 trafficking through Ras-associated binding 8-mediated (RAB8-mediated) exocytosis from the TGN to the plasma membrane, where it bound PD-1 extrinsically to prevent tumor cell killing by T cells. Our findings demonstrate that nonproteolytic ubiquitination of PD-L1 by MIB2 is required for its transportation to the plasma membrane and tumor cell immune evasion.<\/p>\n


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\u7a0b\u5e8f\u6027\u6b7b\u4ea1\u53d7\u4f53\u914d\u4f531 (PD-L1)\u662f\u4e00\u79cd\u91cd\u8981\u7684\u514d\u75ab\u68c0\u67e5\u70b9\u914d\u4f53\uff0c\u5728\u80bf\u7624\u7ec6\u80de\u5185\u8d28\u7f51\u5408\u6210\u5e76\u8f6c\u8fd0\u81f3\u8d28\u819c\uff0c\u4e0eT\u7ec6\u80de\u8868\u9762\u8868\u8fbe\u7684\u7a0b\u5e8f\u6027\u6b7b\u4ea1\u53d7\u4f531 (PD-1)\u76f8\u4e92\u4f5c\u7528\u3002\u8fd9\u79cd\u76f8\u4e92\u4f5c\u7528\u5411T\u7ec6\u80de\u4f20\u9012\u5171\u6291\u5236\u4fe1\u53f7\uff0c\u4ece\u800c\u6291\u5236\u5176\u529f\u80fd\uff0c\u9003\u907f\u6297\u80bf\u7624\u514d\u75ab\u3002\u4e34\u5e8a\u4e0a\u6216\u4e34\u5e8a\u8bd5\u9a8c\u4e2d\u7528\u4e8e\u8bc4\u4f30\u80bf\u7624\u7ec6\u80dePD-L1\u8868\u8fbe\u6c34\u5e73\u7684\u5927\u591a\u6570\u4f34\u968f\u6216\u8865\u5145\u8bca\u65ad\u9700\u8981\u819c\u67d3\u8272\u3002\u7136\u800c\uff0c\u9a71\u52a8PD-L1\u5408\u6210\u540e\u8f6c\u4f4d\u5230\u8d28\u819c\u7684\u673a\u5236\u5c1a\u4e0d\u6e05\u695a\u3002\u5728\u672c\u7814\u7a76\u4e2d\uff0c\u6211\u4eec\u53d1\u73b0MIB2\u662fPD-L1\u4ece\u53cd\u5f0f\u9ad8\u5c14\u57fa\u7f51\u7edc(TGN)\u8f6c\u8fd0\u5230\u764c\u7ec6\u80de\u8d28\u819c\u6240\u5fc5\u9700\u7684\u3002MIB2\u7f3a\u9677\u5bfc\u81f4\u80bf\u7624\u7ec6\u80de\u8868\u9762PD-L1\u86cb\u767d\u51cf\u5c11\uff0c\u5e76\u4fc3\u8fdb\u5c0f\u9f20\u6297\u80bf\u7624\u514d\u75ab\u3002\u5728\u673a\u5236\u4e0a\uff0cMIB2\u50ac\u5316PD-L1\u7684\u975e\u86cb\u767d\u6c34\u89e3\u6027\u6cdb\u7d20\u5316\uff0c\u4fc3\u8fdbPD-L1\u901a\u8fc7Rab8\u4ecb\u5bfc\u7684\u80de\u5410\u4f5c\u7528\u4eceTGN\u8f6c\u8fd0\u81f3\u8d28\u819c\uff0c\u5e76\u5728\u8d28\u819c\u4e0a\u4e0ePD-1\u7ed3\u5408\uff0c\u4ece\u800c\u963b\u6b62T\u7ec6\u80de\u6740\u4f24\u80bf\u7624\u7ec6\u80de\u3002\u6211\u4eec\u7684\u7814\u7a76\u7ed3\u679c\u8868\u660e\uff0cMIB2\u4ecb\u5bfc\u7684PD-L1\u7684\u975e\u86cb\u767d\u6c34\u89e3\u6cdb\u7d20\u5316\u662f\u5176\u8f6c\u8fd0\u5230\u8d28\u819c\u548c\u5f15\u8d77\u80bf\u7624\u7ec6\u80de\u514d\u75ab\u9003\u9038\u6240\u5fc5\u9700\u7684\u3002<\/p>\n


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Keywords:<\/strong><\/p>\n

Cancer; Cancer immunotherapy; Cell Biology; Cellular immune response; Oncology.<\/p>\n

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13<\/strong><\/p>\n<\/section>\n<\/section>\n

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J Clin Invest. 20230201-2<\/strong><\/p>\n<\/section>\n<\/section>\n

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Next-generation antigen-presenting cell immune therapeutics for gliomas<\/strong><\/p>\n

\u9488\u5bf9\u80f6\u8d28\u7624\u7684\u65b0\u4e00\u4ee3\u6297\u539f\u63d0\u5448\u7ec6\u80de\u514d\u75ab\u7597\u6cd5<\/strong><\/span><\/p>\n


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J Clin Invest. 2023 Feb 1;133(3):e163449.<\/em><\/p>\n

doi: <\/strong>10.1172\/JCI163449.<\/p>\n

PubMed:<\/strong> <\/span>https:\/\/pubmed.ncbi.nlm.nih.gov\/36719372\/<\/span><\/p>\n


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Abstract<\/strong><\/p>\n

Antigen presentation machinery and professional antigen-presenting cells (APCs) are fundamental for an efficacious immune response against cancers, especially in the context of T cell-centric immunotherapy. Dendritic cells (DCs), the gold standard APCs, play a crucial role in initiating and maintaining a productive antigen-specific adaptive immunity. In recent decades, ex vivo-differentiated DCs from circulating CD14+ monocytes have become the reference for APC-based immunotherapy. DCs loaded with tumor-associated antigens, synthetic peptides, or RNA activate T cells with antitumor properties. This strategy has paved the way for the development of alternative antigen-presenting vaccination strategies, such as monocytes, B cells, and artificial APCs, that have shown effective therapeutic outcomes in preclinical cancer models. The search for alternative APC platforms was initiated by the overall limited clinical impact of DC vaccines, especially in indications such as gliomas, a primary brain tumor known for resistance to any immune intervention. In this Review, we navigate the APC immune therapeutics’ past, present, and future in the context of primary brain tumors.<\/p>\n


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\u2014 THE  END \u2014<\/span><\/section>\n
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