「抗癌管家」全球肿瘤免疫治疗信息精选【第一期】—抗癌管家( 七 )

Oncology researchers point to one likely culprit for PD-1 resistance: T regulatory cells (Tregs), which are immune cells that limit the ability of so-called killer T cells to destroy cancer. Now, a team led by Sanford Burnham Prebys Medical Discovery Institute is proposing a new way to control Tregs in a way that could boost PD-1 blockers in the treatment of melanoma.
研究人员在小鼠实验中发现，抑制一种名为Siah2的蛋白质可以同时限制T调节细胞的活性，从而使黑素瘤对PD-1抑制剂更加敏感。他们在《Nature》杂志上发表了这项研究。
The researchers showed in mouse models that inhibiting a protein called Siah2 can limit the activity of Tregs, making melanoma tumors sensitive to PD-1 blockade. They published the study in the journal Nature Communications.
实验中发现，没有Siah2的小鼠体内，免疫T细胞数量大大增加，肿瘤也跟着缩小了。有Siah2基因的小鼠体内肿瘤可见明显进展。在施用PD-1抑制剂后，黑色素瘤在缺乏Siah2基因的小鼠体内消失了。
The researchers went on to study tumors from the Siah2 mutant mice and discovered that they were filled with killer T cells. But there were few Tregs in sight.
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来源：《Science Immunology》
发生区域：日本
发布时间：2020.1.31
摘要：EGFR抑制剂当与PD-1单抗药物组合使用时能够提高免疫疗法在肺腺癌中的疗效。
关键字：EGFR、厄洛替尼、PD-1单抗、肺癌
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原文：
科学家在一项新的肿瘤微环境中研究肺癌的表皮生长因子EGFR时发现，抗PD-1药物在EGFR突变时通常是效果不佳的。然而， EGFR抑制剂厄洛替尼若与PD-1单抗药物联用的效果要胜过其中任何一种单独治疗方案，将会在肺腺癌的免疫治疗中起到重要作用。
The clinical efficacy of anti–PD-1 (programmed cell death–1) monoclonal antibody (mAb) against cancers with oncogenic driver gene mutations, which often harbor a low tumor mutation burden, is variable, suggesting different contributions of each driver mutation to immune responses. Here, we investigated the immunological phenotypes in the tumor microenvironment (TME) of epidermal growth factor receptor (EGFR)–mutated lung adenocarcinomas, for which anti–PD-1 mAb is largely ineffective. Whereas EGFR-mutated lung adenocarcinomas had a noninflamed TME, CD4+ effector regulatory T cells, which are generally present in the inflamed TME, showed high infiltration. The EGFR signal activated cJun/cJun N-terminal kinase and reduced interferon regulatory factor–1; the former increased CCL22, which recruits CD4+ regulatory T cells, and the latter decreased CXCL10 and CCL5, which induce CD8+ T cell infiltration. The EGFR inhibitor erlotinib decreased CD4+ effector regulatory T cells infiltration in the TME and in combination with anti–PD-1 mAb showed better antitumor effects than either treatment alone. Our results suggest that EGFR inhibitors when used in conjunction with anti–PD-1 mAb could increase the efficacy of immunotherapy in lung adenocarcinomas.
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来源：《Science》
发生区域：德国
发布时间：2020.1.24