Innate lymphoid cells (ILC) are a family of immune cells that are emerging as potent orchestrators of immune responses. In cancer, ILCs display both pro- and antitumorigenic functions depending on the nature of the tumor and the involved ILC subset. Little is known about the ILC-tumor cross-talk in human melanoma. Here, we showed that ILC1s were enriched but functionally impaired in cytokine secretion in both peripheral blood mononuclear cells and tumor-infiltrated lymph nodes of melanoma patients. These findings were confirmed in vivo in murine cutaneous melanoma. Multiple immunosuppressive mechanisms are described in the melanoma microenvironment. Among others, adenosine and kynurenines were shown to suppress antitumor immune responses. By exposing ILCs to adenosine and kynurenines, we observed a similar shift toward the ILC1 subset distribution and impairment in proinflammatory cytokine production to that of patient samples studied ex vivo Thus, we hypothesized that the immunosuppressive microenvironment of malignant melanoma might shape ILC subpopulations. Hence, we provide a rationale for the use of drugs targeting adenosine and kynurenine pathways in melanoma patients.

中文翻译：

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免疫抑制性调解人损害人类恶性黑色素瘤的促炎性先天淋巴样细胞功能。

先天性淋巴样细胞（ILC）是一类免疫细胞，它们已成为免疫反应的强大协调者。在癌症中，ILC同时显示促癌和抗肿瘤作用，具体取决于肿瘤的性质和所涉及的ILC亚群。关于人类黑素瘤中的ILC-肿瘤串扰知之甚少。在这里，我们表明ILC1s在黑色素瘤患者的外周血单个核细胞和肿瘤浸润的淋巴结中都富含细胞因子，但功能受损。这些发现在小鼠皮肤黑色素瘤体内得到证实。黑色素瘤微环境中描述了多种免疫抑制机制。其中，腺苷和犬尿氨酸可抑制抗肿瘤免疫反应。通过将ILC暴露于腺苷和犬尿氨酸，我们观察到了与体外研究的患者样品类似的向ILC1子集分布和促炎细胞因子产生损害的转变。因此，我们假设恶性黑色素瘤的免疫抑制微环境可能会形成ILC亚群。因此，我们为在黑色素瘤患者中使用靶向腺苷和犬尿氨酸途径的药物提供了理论依据。