Immunoediting instructs tumor metabolic reprogramming to support immune evasion

Chin-Hsien Tsai; Yu-Ming Chuang; Xiaoyun Li; Yi-Ru Yu; Sheue-Fen Tzeng; Shao Thing Teoh; Katherine E Lindblad; Mario Di Matteo; Wan-Chen Cheng; Pei-Chun Hsueh; Kung-Chi Kao; Hana Imrichova; Likun Duan; Hector Gallart-Ayala; Pei-Wen Hsiao; Massimiliano Mazzone; Julijana Ivanesevic; Xiaojing Liu; Karin E de Visser; Amaia Lujambio; Sophia Y Lunt; Susan M Kaech; Ping-Chih Ho

doi:10.1016/j.cmet.2022.12.003

Immunoediting instructs tumor metabolic reprogramming to support immune evasion

Cell Metab. 2023 Jan 3;35(1):118-133.e7. doi: 10.1016/j.cmet.2022.12.003.

Authors

Chin-Hsien Tsai¹, Yu-Ming Chuang², Xiaoyun Li², Yi-Ru Yu², Sheue-Fen Tzeng¹, Shao Thing Teoh³, Katherine E Lindblad⁴, Mario Di Matteo⁵, Wan-Chen Cheng², Pei-Chun Hsueh², Kung-Chi Kao², Hana Imrichova⁶, Likun Duan⁷, Hector Gallart-Ayala⁸, Pei-Wen Hsiao⁹, Massimiliano Mazzone⁵, Julijana Ivanesevic⁶, Xiaojing Liu⁷, Karin E de Visser¹⁰, Amaia Lujambio⁴, Sophia Y Lunt¹¹, Susan M Kaech¹², Ping-Chih Ho¹³

Affiliations

¹ Department of Oncology, University of Lausanne, Lausanne, Switzerland; Ludwig Institute of Cancer Research, University of Lausanne, Lausanne, Switzerland; Graduate Institute of Life Sciences, National Defense Medical Center, Taipei City, Taiwan.
² Department of Oncology, University of Lausanne, Lausanne, Switzerland; Ludwig Institute of Cancer Research, University of Lausanne, Lausanne, Switzerland.
³ Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI, USA.
⁴ Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Liver Cancer Program, Division of Liver Diseases, Department of Medicine, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; The Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Graduate School of Biomedical Sciences at Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁵ Laboratory of Tumor Inflammation and angiogenesis, Vesalius Research Center, VIB, Leuven, Belgium; Laboratory of Tumor Inflammation and angiogenesis, Department of Oncology, KU Leuven, Leuven, Belgium.
⁶ CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Wien, Austria.
⁷ Department of Molecular and Structural Biochemistry, North Carolina State University, Raleigh, NC, USA.
⁸ Metabolomics Platform, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.
⁹ Agricultural Biotechnology Research Center, Academia Sinica, Taipei City, Taiwan.
¹⁰ Division of Tumor Biology and Immunology, Oncode Institute, Netherlands Cancer Institute, Amsterdam, the Netherlands.
¹¹ Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI, USA; Department of Chemical Engineering and Materials Science, Michigan State University, East Lansing, MI, USA.
¹² NOMIS Center for Immunobiology and Microbial Pathogenesis, Salk Institute for Biological Studies, La Jolla, CA, USA.
¹³ Department of Oncology, University of Lausanne, Lausanne, Switzerland; Ludwig Institute of Cancer Research, University of Lausanne, Lausanne, Switzerland. Electronic address: [email protected].

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.

Keywords: IFNγ; Myc; STAT3; immunoediting; immunosurveillance; tumor immunology.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Carcinogenesis
Cell Transformation, Neoplastic
Humans
Immune Evasion*
Interferon-gamma / metabolism
Neoplasms* / pathology
T-Lymphocytes / metabolism
Tumor Microenvironment

Substances

Interferon-gamma

Abstract

Publication types

MeSH terms

Substances

Grants and funding