한빛사논문
Jang Hyun Park1, Hyun-Jin Kim1, Chae Won Kim 1, Hyeon Cheol Kim 1, Yujin Jung 2,
Hyun-Soo Lee2, Yunah Lee1, Young Seok Ju1,3, Ji Eun Oh1,3, Sung-Hong Park2, Jeong Ho Lee1,3, Sung Ki Lee4 and Heung Kyu Lee 1,3 ,*
1Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea.
2Department of Bio and Brain Engineering, KAIST, Daejeon, Republic of Korea.
3BioMedical Research Center, KAIST, Daejeon, Republic of Korea.
4Department of Obstetrics and Gynecology, College of Medicine, Myunggok Medical Research Center, Konyang University, Daejeon, Republic of Korea.
*Corresponding author
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. 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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