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Tumor hypoxia represses γδ T cell-mediated antitumor immunity against brain tumors

ABSTRACT: The anatomic location and immunologic characteristics of brain tumors result in strong lymphocyte suppression. Consequently, conventional immunotherapies targeting CD8 T-cells are ineffective against brain tumors. Tumor cells escape immunosurveillance by various mechanisms, and tumor cell metabolism can affect the metabolic states and functions of tumor-infiltrating lymphocytes. Oxygen tension is one important factor influencing immune responses. Here, we discovered that brain tumor cells had a particularly high demand for oxygen, which affected γδ T-cell-mediated antitumor immune responses but not those of conventional T-cells. Specifically, tumor hypoxia activated the γδ T-cell protein kinase A (PKA) pathway at a transcriptional level, resulting in repression of NKG2D expression. Alleviating tumor hypoxia reinvigorated NKG2D expression and the antitumor function of γδ T-cells. These results reveal a hypoxia-mediated mechanism by which brain tumors and γδ T-cells interact and emphasize the importance of γδ T-cells for antitumor immunity against brain tumors.

ORGANISM(S): Mus musculus

PROVIDER: GSE159542 | GEO | 2020/12/04

REPOSITORIES: GEO

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Tumor hypoxia represses γδ T cell-mediated antitumor immunity against brain tumors

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