Stress relief for cancer immunotherapy: implications for the ER stress response in tumor immunity

被引:14
作者
Andrews, Alex M. [1 ,2 ,3 ]
Tennant, Megan D. [1 ,2 ]
Thaxton, Jessica E. [1 ,2 ,3 ]
机构
[1] Med Univ South Carolina, Dept Orthoped & Phys Med, 68 President St, Charleston, SC 29425 USA
[2] Med Univ South Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA
[3] Hollings Canc Ctr, Charleston, SC 29425 USA
关键词
ER stress; PERK; T cell; Translation; Metabolism; Cancer immunotherapy; ATF4; UNFOLDED PROTEIN RESPONSE; T-CELL MEMORY; INDUCED GENE-EXPRESSION; MESSENGER-RNA; KINASE GCN2; CRITICAL REGULATOR; SREBP ACTIVITY; TRANSLATION; ACTIVATION; METABOLISM;
D O I
10.1007/s00262-020-02740-3
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The solid tumor microenvironment is replete with factors that present a stress to infiltrating immune cells. Endoplasmic reticulum (ER) stress sensor PKR-like ER kinase (PERK) is primed to sense and respond to the burden of misfolded proteins in the ER lumen induced by cell stressors. PERK has documented roles as a master regulator of acute and chronic responses to cell stress as well as in the regulation of cell metabolism. Here, we provide an overview of the roles of PERK based on what is known and remains to be tested in immune cells in tumors and impacts on tumor control. PERK is one of several ER kinases able to preferentially induce activating transcription factor 4 (ATF4) as a response to cell stress. ATF4 orchestrates the oxidative stress response and governs amino acid metabolism. We discuss the tested role of ATF4 in tumor immunity and provide insight on the dueling protective and deleterious roles that ATF4 may play in the stress of solid tumors.
引用
收藏
页码:1165 / 1175
页数:11
相关论文
共 85 条
[1]   THE ROLE OF JUN, FOS AND THE AP-1 COMPLEX IN CELL-PROLIFERATION AND TRANSFORMATION [J].
ANGEL, P ;
KARIN, M .
BIOCHIMICA ET BIOPHYSICA ACTA, 1991, 1072 (2-3) :129-157
[2]   Characterization of a Novel PERK Kinase Inhibitor with Antitumor and Antiangiogenic Activity [J].
Atkins, Charity ;
Liu, Qi ;
Minthorn, Elisabeth ;
Zhang, Shu-Yun ;
Figueroa, David J. ;
Moss, Katherine ;
Stanley, Thomas B. ;
Sanders, Brent ;
Goetz, Aaron ;
Gaul, Nathan ;
Choudhry, Anthony E. ;
Alsaid, Hasan ;
Jucker, Beat M. ;
Axten, Jeffrey M. ;
Kumar, Rakesh .
CANCER RESEARCH, 2013, 73 (06) :1993-2002
[3]   Discovery of 7-Methyl-5-(1-{[3-(trifluoromethyl)phenyl]acetyl}-2,3-dihydro-1H-indol-5-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (GSK2606414), a Potent and Selective First-in-Class Inhibitor of Protein Kinase R (PKR)-like Endoplasmic Reticulum Kinase (PERK) [J].
Axten, Jeffrey M. ;
Medina, Jesus R. ;
Feng, Yanhong ;
Shu, Arthur ;
Romeril, Stuart P. ;
Grant, Seth W. ;
Li, William Hoi Hong ;
Heerding, Dirk A. ;
Minthorn, Elisabeth ;
Mencken, Thomas ;
Atkins, Charity ;
Liu, Qi ;
Rabindran, Sridhar ;
Kumar, Rakesh ;
Hong, Xuan ;
Goetz, Aaron ;
Stanley, Thomas ;
Taylor, J. David ;
Sigethy, Scott D. ;
Tomberlin, Ginger H. ;
Hassell, Annie M. ;
Kahler, Kirsten M. ;
Shewchuk, Lisa M. ;
Gampe, Robert T. .
JOURNAL OF MEDICINAL CHEMISTRY, 2012, 55 (16) :7193-7207
[4]   Dysfunctional T cell metabolism in the tumor microenvironment [J].
Beckermann, Kathryn E. ;
Dudzinski, Stephanie O. ;
Rathmell, Jeffrey C. .
CYTOKINE & GROWTH FACTOR REVIEWS, 2017, 35 :7-14
[5]   Activating transcription factor 4 is translationally regulated by hypoxic stress [J].
Blais, JD ;
Filipenko, V ;
Bi, MX ;
Harding, HP ;
Ron, D ;
Koumenis, C ;
Wouters, BG ;
Bell, JC .
MOLECULAR AND CELLULAR BIOLOGY, 2004, 24 (17) :7469-7482
[6]   PERK-dependent regulation of lipogenesis during mouse mammary gland development and adipocyte differentiation [J].
Bobrovnikova-Marjon, Ekaterina ;
Hatzivassiliou, Georgia ;
Grigoriadou, Christina ;
Romero, Margarita ;
Cavener, Douglas R. ;
Thompson, Craig B. ;
Diehl, J. Alan .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (42) :16314-16319
[7]   PERK Utilizes Intrinsic Lipid Kinase Activity To Generate Phosphatidic Acid, Mediate Akt Activation, and Promote Adipocyte Differentiation [J].
Bobrovnikova-Marjon, Ekaterina ;
Pytel, Dariusz ;
Riese, Matthew J. ;
Vaites, Laura Pontano ;
Singh, Nickpreet ;
Koretzky, Gary A. ;
Witze, Eric S. ;
Diehl, J. Alan .
MOLECULAR AND CELLULAR BIOLOGY, 2012, 32 (12) :2268-2278
[8]   Endoplasmic Reticulum Stress Induces G2 Cell-Cycle Arrest via mRNA Translation of the p53 Isoform p53/47 [J].
Bourougaa, Karima ;
Naski, Nadia ;
Boularan, Cedric ;
Mlynarczyk, Coraline ;
Candeias, Marco M. ;
Marullo, Stefano ;
Fahraeus, Robin .
MOLECULAR CELL, 2010, 38 (01) :78-88
[9]   LDHA-Associated Lactic Acid Production Blunts Tumor Immunosurveillance by T and NK Cells [J].
Brand, Almut ;
Singer, Katrin ;
Koehl, Gudrun E. ;
Kolitzus, Marlene ;
Schoenhammer, Gabriele ;
Thiel, Annette ;
Matos, Carina ;
Bruss, Christina ;
Klobuch, Sebastian ;
Peter, Katrin ;
Kastenberger, Michael ;
Bogdan, Christian ;
Schleicher, Ulrike ;
Mackensen, Andreas ;
Ullrich, Evelyn ;
Fichtner-Feigl, Stefan ;
Kesselring, Rebecca ;
Mack, Matthias ;
Ritter, Uwe ;
Schmid, Maximilian ;
Blank, Christian ;
Dettmer, Katja ;
Oefner, Peter J. ;
Hoffmann, Petra ;
Walenta, Stefan ;
Geissler, Edward K. ;
Pouyssegur, Jacques ;
Villunger, Andreas ;
Steven, Andre ;
Seliger, Barbara ;
Schreml, Stephan ;
Haferkamp, Sebastian ;
Kohl, Elisabeth ;
Karrer, Sigrid ;
Berneburg, Mark ;
Herr, Wolfgang ;
Mueller-Klieser, Wolfgang ;
Renner, Kathrin ;
Kreutz, Marina .
Cell Metabolism, 2016, 24 (05) :657-671
[10]   PERK mediates cell-cycle exit during the mammalian unfolded protein response [J].
Brewer, JW ;
Diehl, JA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (23) :12625-12630