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.
Innate Lymphoid Cells (ILCs) play a key role in tissue mediated immunity and can be controlled by co-receptor 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 mTOR signaling along with increased fatty acid uptake. In line with these metabolic changes, PD-1 deficient Tbet+NK1.1-ILCs expressed significantly increased IFNg, granzyme B and K. Furthermore, PD1 deficient Tbet+NK1.1- ILCs contributed towards diminished tumor growth in an experimental murine model of melanoma. These data demonstrate that PD-1 can regulate anti-tumor responses of Tbet+NK1.1-ILCs within the tumor microenvironment.
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