Programmed cell death-1 receptor-mediated regulation of Tbet + NK1.1 innate lymphoid cells within the tumor microenvironment

Proceedings of the National Academy of Sciences of the United States of America(2023)

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摘要
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.
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关键词
lymphoid cells,tumor microenvironment,tbet,receptor-mediated
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