1. Immunoediting instructs tumor metabolic reprogramming to support immune evasion.
- Author
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Tsai CH, Chuang YM, Li X, Yu YR, Tzeng SF, Teoh ST, Lindblad KE, Di Matteo M, Cheng WC, Hsueh PC, Kao KC, Imrichova H, Duan L, Gallart-Ayala H, Hsiao PW, Mazzone M, Ivanesevic J, Liu X, de Visser KE, Lujambio A, Lunt SY, Kaech SM, and Ho PC
- Subjects
- Humans, Interferon-gamma metabolism, T-Lymphocytes metabolism, Carcinogenesis, Cell Transformation, Neoplastic, Tumor Microenvironment, Immune Evasion, Neoplasms pathology
- Abstract
Immunoediting sculpts immunogenicity and thwarts host anti-tumor responses in tumor cells during tumorigenesis; however, it remains unknown whether metabolic programming of tumor cells can be guided by immunosurveillance. Here, we report that T cell-mediated immunosurveillance in early-stage tumorigenesis instructs c-Myc upregulation and metabolic reprogramming in tumor cells. This previously unexplored tumor-immune interaction is controlled by non-canonical interferon gamma (IFNγ)-STAT3 signaling and supports tumor immune evasion. Our findings uncover that immunoediting instructs deregulated bioenergetic programs in tumor cells to empower them to disarm the T cell-mediated immunosurveillance by imposing metabolic tug-of-war between tumor and infiltrating T cells and forming the suppressive tumor microenvironment., Competing Interests: Declaration of interests P.-C.H. is a member of the scientific advisory board for Elixiron Immunotherapeutics and received research grants from Elixiron Immunotherapeutics. P.-C.H. is also a founder of Pilatus Biosciences., (Copyright © 2022 Elsevier Inc. All rights reserved.)
- Published
- 2023
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