INSERM U1231, Equipe Labellisée Ligue Contre le Cancer, Dijon, France.
Cancer Biology Transfer Platform, Georges-Francois Leclerc Cancer Center-UNICANCER, Dijon, France.
Nat Immunol. 2022 Feb;23(2):262-274. doi: 10.1038/s41590-021-01120-y. Epub 2022 Jan 31.
Tumors poorly infiltrated by T cells are more resistant to immunogenic chemotherapies and checkpoint inhibition than highly infiltrated tumors. Using murine models, we found that CCR6 type 3 innate lymphoid cells (ILC3s) can trigger an increase in the number of T cells infiltrating a tumor. Shortly after administration of cisplatin chemotherapy, production of the chemokine CCL20 and proinflammatory cytokine IL-1β at the tumor site led to the recruitment and activation of ILC3s. Within the tumor, ILC3 production of the chemokine CXCL10 was responsible for the recruitment of CD4 and CD8 T lymphocytes to the tumor. ILC3-dependent infiltration of T cells was essential for antitumor immune responses and increased the efficacy of checkpoint inhibition. Thus, we reveal an essential role of CCL20 and IL-1β, which promote ILC3-dependent antitumor immunity and enhance tumor sensitivity to immunotherapy.
肿瘤中 T 细胞浸润不良的比高度浸润的肿瘤对免疫化疗和检查点抑制更具抵抗力。使用小鼠模型，我们发现 CCR6 型 3 先天淋巴样细胞（ILC3）可以触发浸润肿瘤的 T 细胞数量增加。在顺铂化疗后不久，肿瘤部位趋化因子 CCL20 和促炎细胞因子 IL-1β 的产生导致 ILC3 的募集和激活。在肿瘤内，趋化因子 CXCL10 的 ILC3 产生负责将 CD4 和 CD8 T 淋巴细胞募集到肿瘤中。ILC3 依赖性 T 细胞浸润对于抗肿瘤免疫反应至关重要，并增加了检查点抑制的疗效。因此，我们揭示了 CCL20 和 IL-1β 的重要作用，它们促进了 ILC3 依赖性抗肿瘤免疫并增强了肿瘤对免疫治疗的敏感性。
