@article{5399a7bc6bb84be092b104d55bf7c6ce,
title = "Tumor-associated macrophages expressing the transcription factor IRF8 promote T cell exhaustion in cancer",
abstract = "Tumors are populated by antigen-presenting cells (APCs) including macrophage subsets with distinct origins and functions. Here, we examined how cancer impacts mononuclear phagocytic APCs in a murine model of breast cancer. Tumors induced the expansion of monocyte-derived tumor-associated macrophages (TAMs) and the activation of type 1 dendritic cells (DC1s), both of which expressed and required the transcription factor interferon regulatory factor-8 (IRF8). Although DC1s mediated cytotoxic T lymphocyte (CTL) priming in tumor-draining lymph nodes, TAMs promoted CTL exhaustion in the tumor, and IRF8 was required for TAMs{\textquoteright} ability to present cancer cell antigens. TAM-specific IRF8 deletion prevented exhaustion of cancer-cell-reactive CTLs and suppressed tumor growth. Tumors from patients with immune-infiltrated renal cell carcinoma had abundant TAMs that expressed IRF8 and were enriched for an IRF8 gene expression signature. Furthermore, the TAM-IRF8 signature co-segregated with CTL exhaustion signatures across multiple cancer types. Thus, CTL exhaustion is promoted by TAMs via IRF8.",
keywords = "IRF8, T cell exhaustion, antigen presentation, antigen-presenting cell, tumor-associated macrophage",
author = "Nixon, {Briana G.} and Fengshen Kuo and Ji, {Liang Liang} and Ming Liu and Kristelle Capistrano and Mytrang Do and Franklin, {Ruth A.} and Xiaodi Wu and Kansler, {Emily R.} and Srivastava, {Raghvendra M.} and Purohit, {Tanaya A.} and Alejandro Sanchez and Lynda Vuong and Chirag Krishna and Xinxin Wang and Morse, {Herbert C.} and Hsieh, {James J.} and Chan, {Timothy A.} and Murphy, {Kenneth M.} and Moon, {James J.} and Hakimi, {A. Ari} and Li, {Ming O.}",
note = "Funding Information: We acknowledge the use of the Integrated Genomics Operation Core funded by the NCI Cancer Center Support Grant (CCSG, P30 CA08748 ), Cycle for Survival , and the Marie-Jos{\'e}e and Henry R. Kravis Center for Molecular Oncology . This work was supported by the National Institutes of Health ( F31 CA210332 to B.G.N. and R01 CA198280 to M.O.L.), the Howard Hughes Medical Institute ( Faculty Scholar Award to M.O.L.), the Alan and Sandra Gerry Metastasis and Tumor Ecosystems Center (M.O.L.), the Ludwig Center (A.A.H.), the Parker Institute (A.A.H.), and the Weiss Family Foundation (A.A.H.). Publisher Copyright: {\textcopyright} 2022 Elsevier Inc.",
year = "2022",
month = nov,
day = "8",
doi = "10.1016/j.immuni.2022.10.002",
language = "English",
volume = "55",
pages = "2044--2058.e5",
journal = "Immunity",
issn = "1074-7613",
number = "11",
}