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Park, Jang Hyun; Kim, Hyun-Jin; Kim, Chae Won; Kim, Hyeon Cheol; Jung, Yujin; Lee, Hyun-Soo; Lee, Yunah; Ju, Young Seok; Oh, Ji Eun; Park, Sung-Hong; Lee, Jeong Ho; Lee, Sung Ki; Lee, Heung Kyu
Nature immunology, 03/2021, Letnik: 22, Številka: 3Journal Article
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. 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 pathway at a transcriptional level, resulting in repression of the activatory receptor NKG2D. Alleviating tumor hypoxia reinvigorated NKG2D expression and the antitumor function of γδ T cells. These results reveal a hypoxia-mediated mechanism through which brain tumors and γδ T cells interact and emphasize the importance of γδ T cells for antitumor immunity against brain tumors.
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in: SICRIS
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