Year: 2019
Type: article
Abstract: Autophagy is a cell survival process essential for the regulation of immune responses to infections. However, the role of T cell autophagy in anti-tumor immunity is less clear. Here, we demonstrate a cell-autonomous role for autophagy in the regulation of CD8 + T-cell-mediated control of tumors. Mice deficient for the essential autophagy genes Atg5 , Atg14 , or Atg16L1 display a dramatic impairment in the growth of syngeneic tumors. Moreover, T cells lacking Atg5 have a profound shift to an effector memory phenotype and produce greater amounts of interferon-γ (IFN-γ) and tumor necrosis factor α (TNF-α). Mechanistically, Atg5 −/− CD8 + T cells exhibit enhanced glucose metabolism that results in alterations in histone methylation, increases in H3K4me3 density, and transcriptional upregulation of both metabolic and effector target genes. Nonetheless, glucose restriction is sufficient to suppress Atg5-dependent increases in effector function. Thus, autophagy-dependent changes in CD8 + T cell metabolism directly regulate anti-tumor immunity.
Source: Cell Reports
Authors: Lindsay DeVorkin, Nils Pavey, Gillian Carleton, Alexandra Comber, Cally Ho, Junghyun Lim, Erin McNamara, Haochu Huang, Paul Kim, Lauren G. Zacharias, Noboru Mizushima, Tatsuya Saitoh, Shizuo Akira, Wayne Beckham, Alireza Lorzadeh, Michelle Moksa, Qi Cao, Aditya Murthy, Martin Hirst, Ralph J. DeBerardinis, Julian J. Lum
Institutions: BC Cancer – Victoria, University of Victoria, Genentech, Children's Medical Center, The University of Texas Southwestern Medical Center, The University of Tokyo, Tokushima University, Immunology Frontier Research Center, The University of Osaka, The University of Osaka, University of British Columbia, Canada's Michael Smith Genome Sciences Centre
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,200
Awards: Understanding and chemical control of sterile inflammation, Understanding and chemical control of inflammasome-mediated inflammation, G2694566742, Understanding of innate immune system-mediated inflammatory response regulated by bioactive lipids, G5505609052, Identification of nutrient-sensing system that promotes host defense responses
OpenAlex ID: W2937057550