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.

免疫系统可以抑制恶性肿瘤。然而，免疫监视反应的类别及其肿瘤感知模式仍未完全了解。在这里，我们表明虽然透明细胞肾细胞癌 (ccRCC) 被耗竭表型 CD8 ^+浸润与患者预后呈负相关的 T 细胞，嫌色细胞 RCC (chRCC) 大量浸润表达颗粒酶 A 的上皮内 1 型先天性淋巴样细胞 (ILC1s)，这与患者生存呈正相关。白细胞介素 15 (IL-15) 促进 ILC1 颗粒酶 A 表达和细胞毒性，并且 chRCC 肿瘤组织中的 IL-15 表达与 ILC1 反应呈正相关。ILC1 基因特征还预测了与 IL-15 表达相关的一部分乳腺癌患者的存活率。值得注意的是，ILC1s 直接与癌细胞相互作用，癌细胞产生的 IL-15 支持 ILC1s 在小鼠乳腺癌模型中的扩增和抗肿瘤功能。因此，癌细胞 IL-15 的 ILC1 感应定义了上皮恶性肿瘤的免疫监视机制。