固有淋巴样细胞（ILCs）在组织介导的免疫中起着关键作用，并可以通过共受体信号进行控制。在这里，我们定义了一种Tbet + NK1.1-的ILCs子集，并存在于肿瘤微环境中（TME）。我们展示了PD-1受体在TME内的ILCs上表达，并在Tbet + NK1.1- ILCs中发现了PD-1。在多个小鼠和人类肿瘤中，PD-1显着控制了Tbet + NK1.1- ILCs的增殖和功能。我们发现，肿瘤衍生的乳酸增强了TME内Tbet + NK1.1- ILCs上的PD-1表达，这导致了哺乳动物雷帕霉素（mTOR）信号的抑制以及脂肪酸的摄取增加。与这些代谢变化一致，PD-1缺陷的Tbet + NK1.1- ILCs表达了明显增加的IFNγ和肉碱酸B和K。此外，在一个黑色素瘤的小鼠实验模型中，PD-1缺陷的Tbet + NK1.1- ILCs导致了肿瘤生长减缓。这些数据表明，PD-1可以调节TME中Tbet + NK1.1- ILCs的抗肿瘤反应。

Innate lymphoid cells (ILCs) play a key role in tissue-mediated immunity and can be controlled by coreceptor signaling. Here, we define a subset of ILCs that are Tbet+NK1.1- and are present within the tumor microenvironment (TME). We show programmed death-1 receptor (PD-1) expression on ILCs within TME is found in Tbet+NK1.1- ILCs. PD-1 significantly controlled the proliferation and function of Tbet+NK1.1- ILCs in multiple murine and human tumors. We found tumor-derived lactate enhanced PD-1 expression on Tbet+NK1.1- ILCs within the TME, which resulted in dampened the mammalian target of rapamycin (mTOR) signaling along with increased fatty acid uptake. In line with these metabolic changes, PD-1-deficient Tbet+NK1.1- ILCs expressed significantly increased IFNγ and granzyme B and K. Furthermore, PD-1-deficient Tbet+NK1.1- ILCs contributed toward diminished tumor growth in an experimental murine model of melanoma. These data demonstrate that PD-1 can regulate antitumor responses of Tbet+NK1.1- ILCs within the TME.