美国纪念斯隆-凯特琳癌症中心李明研究组发现，细胞毒性先天性淋巴细胞感知癌细胞表达的白细胞介素-15来抑制人类和小鼠的恶性肿瘤。2022年5月26日，国际知名学术期刊《自然—免疫学》在线发表了这一成果。

研究人员发现，尽管透明细胞肾细胞癌（ccRCC）被耗竭型CD8⁺T细胞浸润，与患者的预后呈负相关，但嫌色细胞型肾细胞癌（chRCC）有大量表达颗粒酶A的上皮内1型先天淋巴细胞（ILC1）浸润，与患者的生存率呈正相关。白细胞介素-15（IL-15）促进ILC1颗粒酶A的表达和细胞毒性，IL-15在chRCC肿瘤组织中的表达与ILC1的反应呈正相关。ILC1基因特征也预测了与IL-15表达有关的乳腺癌患者亚群的生存率。

值得注意的是，ILC1直接与癌细胞相互作用，而癌细胞产生的IL-15支持ILC1s在小鼠乳腺癌模型中的扩张和抗肿瘤功能。因此，ILC1对癌细胞IL-15的感应确定了上皮性恶性肿瘤的免疫监视机制。

据介绍，恶性肿瘤可以被免疫系统所抑制。然而，对免疫监视反应的类别和它们对肿瘤的感应模式仍不完全了解。

附：英文原文

Title: Cytotoxic innate lymphoid cells sense cancer cell-expressed interleukin-15 to suppress human and murine malignancies

Author: Kansler, Emily R., Dadi, Sada, Krishna, Chirag, Nixon, Briana G., Stamatiades, Efstathios G., Liu, Ming, Kuo, Fengshen, Zhang, Jing, Zhang, Xian, Capistrano, Kristelle, Blum, Kyle A., Weiss, Kate, Kedl, Ross M., Cui, Guangwei, Ikuta, Koichi, Chan, Timothy A., Leslie, Christina S., Hakimi, A. Ari, Li, Ming O.

Issue&Volume: 2022-05-26

Abstract: Malignancy can be suppressed by the immune system. However, the classes of immunosurveillance responses and their mode of tumor sensing remain incompletely understood. Here, we show that although clear cell renal cell carcinoma (ccRCC) was infiltrated by exhaustion-phenotype CD8+ T cells that negatively correlated with patient prognosis, chromophobe RCC (chRCC) had abundant infiltration of granzyme A-expressing intraepithelial type 1 innate lymphoid cells (ILC1s) that positively associated with patient survival. Interleukin-15 (IL-15) promoted ILC1 granzyme A expression and cytotoxicity, and IL-15 expression in chRCC tumor tissue positively tracked with the ILC1 response. An ILC1 gene signature also predicted survival of a subset of breast cancer patients in association with IL-15 expression. Notably, ILC1s directly interacted with cancer cells, and IL-15 produced by cancer cells supported the expansion and anti-tumor function of ILC1s in a murine breast cancer model. Thus, ILC1 sensing of cancer cell IL-15 defines an immunosurveillance mechanism of epithelial malignancies. How the immune system responds to epithelial cancers beyond neoantigen-driven adaptive immunity is poorly understood. Kansler et al. reveal an innate immune surveillance response mediated by cytotoxic ILC1 sensing of cancer cell-expressed IL-15.

DOI: 10.1038/s41590-022-01213-2

Source: https://www.nature.com/articles/s41590-022-01213-2