The acidity of the tumor microenvironment is a mechanism of immune escape that can be overcome by proton pump inhibitors

被引:122
作者
Bellone, Matteo [1 ]
Calcinotto, Arianna [1 ]
Filipazzi, Paola [2 ]
De Milito, Angelo [3 ,4 ]
Fais, Stefano [3 ]
Rivoltini, Licia [2 ]
机构
[1] Ist Sci San Raffaele, Cellular Immunol Unit, I-20132 Milan, Italy
[2] Fdn IRCCS Ist Nazl Tumori, Unit Immunotherapy Human Tumors, Milan, Italy
[3] Ist Super Sanita, Dept Therapeut Res & Med Evaluat, Unit Antitumor Drugs, I-00161 Rome, Italy
[4] Karolinska Inst, Canc Ctr Karolinska, Stockholm, Sweden
关键词
anergy; T cell; melanoma; prostate cancer; adoptive immunotherapy; active immunotherapy; CELLS;
D O I
10.4161/onci.22058
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
We have recently reported that lowering the pH to values that are frequently detected in tumors causes reversible anergy in both human and mouse CD8(+) T lymphocytes in vitro. The same occurs in vivo, in the tumor microenvironment and the administration of proton pump inhibitors, which buffer tumor acidity, can revert T-cell anergy and increase the efficacy of immunotherapy.
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页数:3
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共 10 条
[1]   Regulation of cancer cell metabolism [J].
Cairns, Rob A. ;
Harris, Isaac S. ;
Mak, Tak W. .
NATURE REVIEWS CANCER, 2011, 11 (02) :85-95
[2]   Modulation of Microenvironment Acidity Reverses Anergy in Human and Murine Tumor-Infiltrating T Lymphocytes [J].
Calcinotto, Arianna ;
Filipazzi, Paola ;
Grioni, Matteo ;
Iero, Manuela ;
De Milito, Angelo ;
Ricupito, Alessia ;
Cova, Agata ;
Canese, Rossella ;
Jachetti, Elena ;
Rossetti, Monica ;
Huber, Veronica ;
Parmiani, Giorgio ;
Generoso, Luca ;
Santinami, Mario ;
Borghi, Martina ;
Fais, Stefano ;
Bellone, Matteo ;
Rivoltini, Licia .
CANCER RESEARCH, 2012, 72 (11) :2746-2756
[3]   Inhibitory effect of tumor cell-derived lactic acid on human T cells [J].
Fischer, Karin ;
Hoffmann, Petra ;
Voelkl, Simon ;
Meidenbauer, Norbert ;
Ammer, Julia ;
Edinger, Matthias ;
Gottfried, Eva ;
Schwarz, Sabine ;
Rothe, Gregor ;
Hoves, Sabine ;
Renner, Kathrin ;
Timischl, Birgit ;
Mackensen, Andreas ;
Kunz-Schughart, Leoni ;
Andreesen, Reinhard ;
Krause, Stefan W. ;
Kreutz, Marina .
BLOOD, 2007, 109 (09) :3812-3819
[4]   Why do cancers have high aerobic glycolysis? [J].
Gatenby, RA ;
Gillies, RJ .
NATURE REVIEWS CANCER, 2004, 4 (11) :891-899
[5]   Relevance of tumor microenvironment for progression, therapy and drug development [J].
Henning, T ;
Kraus, M ;
Brischwein, M ;
Otto, AM ;
Wolf, B .
ANTI-CANCER DRUGS, 2004, 15 (01) :7-14
[6]  
Lardner A, 2001, J LEUKOCYTE BIOL, V69, P522
[7]   Proton pump inhibitors: actions and reactions [J].
Mullin, James M. ;
Gabello, Melissa ;
Murray, Lisa J. ;
Farrell, Christopher P. ;
Bellows, Jillan ;
Wolov, Kevin R. ;
Kearney, Keith R. ;
Rudolph, David ;
Thornton, James J. .
DRUG DISCOVERY TODAY, 2009, 14 (13-14) :647-660
[8]   A proton-pump inhibitor expedition: The case histories of omeprazole and esomeprazole [J].
Olbe, L ;
Carlsson, E ;
Lindberg, P .
NATURE REVIEWS DRUG DISCOVERY, 2003, 2 (02) :132-139
[9]   Immunosuppressive strategies that are mediated by tumor cells [J].
Rabinovich, Gabriel A. ;
Gabrilovich, Dmitry ;
Sotomayor, Eduardo M. .
ANNUAL REVIEW OF IMMUNOLOGY, 2007, 25 :267-296
[10]   Immunopotentiating effect of proton pump inhibitor pantoprazole in a lymphoma-bearing murine host Implication in antitumor activation of tumor-associated macrophages [J].
Vishvakarma, Naveen Kumar ;
Singh, Sukh Mahendra .
IMMUNOLOGY LETTERS, 2010, 134 (01) :83-92