Tumor cell–originated events prevent efficient antitumor immune response and limit the application of anti-PD1 checkpoint immunotherapy. We show that syndecan-1 (SDC1) has a critical role in the regulation of T cell–mediated control of tumor growth. SDC1 inhibition increases the permeation of CD8 + T cells into tumors and triggers CD8 + T cell–mediated control of tumor growth, accompanied by increased proportions of progenitor-exhausted and effector-like CD8 + T cells. SDC1 deficiency alters multiple signaling events in tumor cells, including enhanced IFN-γ–STAT1 signaling, and augments antigen presentation and sensitivity to T cell–mediated cytotoxicity. Combinatory inhibition of SDC1 markedly potentiates the therapeutic effects of anti-PD1 in inhibiting tumor growth. Consistently, the findings are supported by the data from human tumors showing that SDC1 expression negatively correlates with T cell presence in tumor tissues and the response to immune checkpoint blockade therapy. Our findings suggest that SDC1 inhibits antitumor immunity, and that targeting SDC1 may promote anti-PD1 response for cancer treatment.

中文翻译：

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Syndecan-1 抑制促进抗肿瘤免疫反应并促进抗 PD1 检查点免疫治疗的疗效


肿瘤细胞起源的事件会阻止有效的抗肿瘤免疫反应，并限制抗 PD1 检查点免疫疗法的应用。我们表明 syndecan-1 （SDC1） 在调节 T 细胞介导的肿瘤生长控制中起关键作用。SDC1 抑制增加 CD8 + T 细胞向肿瘤的渗透，并触发 CD8 + T 细胞介导的肿瘤生长控制，同时祖细胞耗竭和效应样 CD8 + T 细胞的比例增加。SDC1 缺陷会改变肿瘤细胞中的多个信号转导事件，包括增强的 IFN-γ-STAT1 信号转导，并增强抗原呈递和对 T 细胞介导的细胞毒性的敏感性。SDC1 的组合抑制显着增强了抗 PD1 在抑制肿瘤生长方面的治疗作用。一致的是，这些发现得到了人类肿瘤数据的支持，这些数据表明 SDC1 表达与肿瘤组织中 T 细胞的存在和对免疫检查点阻断治疗的反应呈负相关。我们的研究结果表明，SDC1 抑制抗肿瘤免疫，靶向 SDC1 可能会促进癌症治疗的抗 PD1 反应。