@article{208a30bdb457438aafb41be20a4730f3,
title = "Immunoediting instructs tumor metabolic reprogramming to support immune evasion",
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",
author = "Tsai, {Chin Hsien} and Chuang, {Yu Ming} and Xiaoyun Li and Yu, {Yi Ru} and Tzeng, {Sheue Fen} and Teoh, {Shao Thing} and Lindblad, {Katherine E.} and {Di Matteo}, Mario and Cheng, {Wan Chen} and Hsueh, {Pei Chun} and Kao, {Kung Chi} and Hana Imrichova and Likun Duan and Hector Gallart-Ayala and Hsiao, {Pei Wen} and Massimiliano Mazzone and Julijana Ivanesevic and Xiaojing Liu and {de Visser}, {Karin E.} and Amaia Lujambio and Lunt, {Sophia Y.} and Kaech, {Susan M.} and Ho, {Ping Chih}",
note = "Funding Information: We thank Li-Fan Lu and Stanley Ching-Cheng Huang for providing valuable comments. P.-C. Hsueh is funded by the European Research Council starting grant ( 802773-MitoGuide ), SNSF grants ( 31003A_182470 , CRSII5_205930 , and IZLCZ0_206083 ), the Cancer Research Institute ( CLIP and Lloyd J. Old STAR award ), the Melanoma Research Alliance Young and Established Investigator Awards , EMBO Young Investigator Award , and Ludwig Cancer Research . C.-H.T. is supported in part by Ministry of Science and Technology (MOST 111-2314-B-016-004 ), Instrument Center of National Defense Medical Center , and Agricultural Biotechnology Research Center . Y.-M.C. and P.-C.H. are supported in part by Ministry of Science and Technology Taiwan , and P.-W.H. is supported by Academia Sinica . J.I. is supported by SNSF R'Equip 316030_183377 . X. Li and X. Liu are supported by North Carolina State University startup fund. A.L. was supported by a Damon Runyon-Rachleff Innovation Award ( DR52-18 ) and R37 Merit Award ( R37CA230636 ). S.Y.L. acknowledges funding from the METAvivor Early Career Investigator Grant and the American Association for Cancer Research-Incyte NextGen Grant for Transformative Cancer Research . S.M.K. is supported by the NIH ( R01 CA206483 ), the Melanoma Research Alliance, and a Salk innovation grant . Funding Information: We thank Li-Fan Lu and Stanley Ching-Cheng Huang for providing valuable comments. P.-C. Hsueh is funded by the European Research Council starting grant (802773-MitoGuide), SNSF grants (31003A_182470, CRSII5_205930, and IZLCZ0_206083), the Cancer Research Institute (CLIP and Lloyd J. Old STAR award), the Melanoma Research Alliance Young and Established Investigator Awards, EMBO Young Investigator Award, and Ludwig Cancer Research. C.-H.T. is supported in part by Ministry of Science and Technology (MOST 111-2314-B-016-004), Instrument Center of National Defense Medical Center, and Agricultural Biotechnology Research Center. Y.-M.C. and P.-C.H. are supported in part by Ministry of Science and Technology Taiwan, and P.-W.H. is supported by Academia Sinica. J.I. is supported by SNSF R'Equip 316030_183377. X. Li and X. Liu are supported by North Carolina State University startup fund. A.L. was supported by a Damon Runyon-Rachleff Innovation Award (DR52-18) and R37 Merit Award (R37CA230636). S.Y.L. acknowledges funding from the METAvivor Early Career Investigator Grant and the American Association for Cancer Research-Incyte NextGen Grant for Transformative Cancer Research. S.M.K. is supported by the NIH (R01 CA206483), the Melanoma Research Alliance, and a Salk innovation grant. C.-H.T. S.M.K. and P.-C. Ho contributed to overall project design and wrote manuscript. C.-H.T. Y.-M.C. X. Li, Y.-R.Y. S.-F.T. K.E.L. W.-C.C. and K.-C.K. performed in vitro and in vivo animal works and data analysis with melanoma models. Y.-M.C. and H.I. performed analysis of sequencing results and TCGA analyses. S.T.T. P.-C. Hsueh, L.D. and H.G.-A. conducted metabolomics analyses under the supervision of S.Y.L. X. Liu, J.I. and P.-C. Ho. M.D.M. M.M. K.E.d.V. and A.L. provided reagents, the primary tumor cells, and tumor samples from genetically engineered murine tumor models. 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. We support inclusive, diverse, and equitable conduct of research. Publisher Copyright: {\textcopyright} 2022 Elsevier Inc.",
year = "2023",
month = jan,
day = "3",
doi = "10.1016/j.cmet.2022.12.003",
language = "English",
volume = "35",
pages = "118--133.e7",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "1",
}