Immunometabolism of regulatory T cells in cancer

被引:0
作者
Saravia, Jordy [1 ]
Chi, Hongbo [1 ]
机构
[1] St Jude Childrens Res Hosp, Dept Immunol, Memphis, TN 38105 USA
基金
美国国家卫生研究院;
关键词
TUMOR-ASSOCIATED MACROPHAGES; TRANSCRIPTION-FACTOR; ANTITUMOR IMMUNITY; DENDRITIC CELLS; HYPOXIA; FOXP3; METABOLISM; CHECKPOINT; EXPRESSION; IMMUNOSUPPRESSION;
D O I
10.1038/s41388-025-03458-1
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Regulatory T (Treg) cells play critical roles in maintaining immune tolerance and tissue homeostasis, but impede anti-tumor immunity. Recent work has established how Treg cells metabolically adapt within the tumor microenvironment (TME), and these adaptations frequently provide a functional advantage over effector T cells. Further, enhanced Treg cell function in the TME may contribute to the limited efficacy of current immunotherapies, especially immune checkpoint blockade (ICB). Here, we review recent progress in understanding mechanisms of Treg cell heterogeneity and function in tumors, with a particular focus on cellular metabolism as an underlying factor by which Treg cells are uniquely poised to thrive in the TME and contribute to tumorigenesis. We describe how cellular metabolism and nutrient or metabolic communication shape Treg cell lineage identity and function in the TME. We also discuss the interplay between ICB and Treg cell metabolism and function, and highlight current strategies targeting Treg cell metabolism specifically in the TME. Understanding metabolic control of intratumoral Treg cells provides excellent opportunities to uncover new or combination therapies for cancer.
引用
收藏
页码:2011 / 2024
页数:14
相关论文
共 219 条
[31]   Hypoxia-inducible factor-1 alpha-dependent induction of FoxP3 drives regulatory T-cell abundance and function during inflammatory hypoxia of the mucosa [J].
Clambey, Eric T. ;
McNamee, Eoin N. ;
Westrich, Joseph A. ;
Glover, Louise E. ;
Campbell, Eric L. ;
Jedlicka, Paul ;
de Zoeten, Edwin F. ;
Cambier, John C. ;
Stenmark, Kurt R. ;
Colgan, Sean P. ;
Eltzschig, Holger K. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2012, 109 (41) :E2784-E2793
[32]   Functional polarization of tumour-associated macrophages by tumour-derived lactic acid [J].
Colegio, Oscar R. ;
Ngoc-Quynh Chu ;
Szabo, Alison L. ;
Chu, Thach ;
Rhebergen, Anne Marie ;
Jairam, Vikram ;
Cyrus, Nika ;
Brokowski, Carolyn E. ;
Eisenbarth, Stephanie C. ;
Phillips, Gillian M. ;
Cline, Gary W. ;
Phillips, Andrew J. ;
Medzhitov, Ruslan .
NATURE, 2014, 513 (7519) :559-+
[33]   FOXP3 expression diversifies the metabolic capacity and enhances the efficacy of CD8 T cells in adoptive immunotherapy of melanoma [J].
Conde, Enrique ;
Casares, Noelia ;
Mancheno, Uxua ;
Elizalde, Edurne ;
Vercher, Enric ;
Capozzi, Roberto ;
Santamaria, Eva ;
Rodriguez-Madoz, Juan R. ;
Prosper, Felipe ;
Lasarte, Juan J. ;
Lozano, Teresa ;
Hervas-Stubbs, Sandra .
MOLECULAR THERAPY, 2023, 31 (01) :48-65
[34]   Systemic short chain fatty acids limit antitumor effect of CTLA-4 blockade in hosts with cancer [J].
Coutzac, Clelia ;
Jouniaux, Jean-Mehdi ;
Paci, Angelo ;
Schmidt, Julien ;
Mallardo, Domenico ;
Seck, Atmane ;
Asvatourian, Vahe ;
Cassard, Lydie ;
Saulnier, Patrick ;
Lacroix, Ludovic ;
Woerther, Paul-Louis ;
Vozy, Aurore ;
Naigeon, Marie ;
Nebot-Bral, Laetitia ;
Desbois, Melanie ;
Simeone, Ester ;
Mateus, Christine ;
Boselli, Lisa ;
Grivel, Jonathan ;
Soularue, Emilie ;
Lepage, Patricia ;
Carbonnel, Franck ;
Ascierto, Paolo Antonio ;
Robert, Caroline ;
Chaput, Nathalie .
NATURE COMMUNICATIONS, 2020, 11 (01)
[35]   Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival [J].
Curiel, TJ ;
Coukos, G ;
Zou, LH ;
Alvarez, X ;
Cheng, P ;
Mottram, P ;
Evdemon-Hogan, M ;
Conejo-Garcia, JR ;
Zhang, L ;
Burow, M ;
Zhu, Y ;
Wei, S ;
Kryczek, I ;
Daniel, B ;
Gordon, A ;
Myers, L ;
Lackner, A ;
Disis, ML ;
Knutson, KL ;
Chen, LP ;
Zou, WP .
NATURE MEDICINE, 2004, 10 (09) :942-949
[36]   Control of TH17/Treg Balance by Hypoxia-Inducible Factor 1 [J].
Dang, Eric V. ;
Barbi, Joseph ;
Yang, Huang-Yu ;
Jinasena, Dilini ;
Yu, Hong ;
Zheng, Ying ;
Bordman, Zachary ;
Fu, Juan ;
Kim, Young ;
Yen, Hung-Rong ;
Luo, Weibo ;
Zeller, Karen ;
Shimoda, Larissa ;
Topalian, Suzanne L. ;
Semenza, Gregg L. ;
Dang, Chi V. ;
Pardoll, Drew M. ;
Pan, Fan .
CELL, 2011, 146 (05) :772-784
[37]   Glycolysis controls the induction of human regulatory T cells by modulating the expression of FOXP3 exon 2 splicing variants [J].
De Rosa, Veronica ;
Galgani, Mario ;
Porcellini, Antonio ;
Colamatteo, Alessandra ;
Santopaolo, Marianna ;
Zuchegna, Candida ;
Romano, Antonella ;
De Simone, Salvatore ;
Procaccini, Claudio ;
La Rocca, Claudia ;
Carrieri, Pietro Biagio ;
Maniscalco, Giorgia Teresa ;
Salvetti, Marco ;
Buscarinu, Maria Chiara ;
Franzese, Adriana ;
Mozzillo, Enza ;
La Cava, Antonio ;
Matarese, Giuseppe .
NATURE IMMUNOLOGY, 2015, 16 (11) :1174-1184
[38]   Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression [J].
Deaglio, Silvia ;
Dwyer, Karen M. ;
Gao, Wenda ;
Friedman, David ;
Usheva, Anny ;
Erat, Anna ;
Chen, Jiang-Fan ;
Enjyoji, Keiichii ;
Linden, Joel ;
Oukka, Mohamed ;
Kuchroo, Vijay K. ;
Strom, Terry B. ;
Robson, Simon C. .
JOURNAL OF EXPERIMENTAL MEDICINE, 2007, 204 (06) :1257-1265
[39]   Visceral Adipose Inflammation in Obesity Is Associated with Critical Alterations in Tregulatory Cell Numbers [J].
Deiuliis, Jeffrey ;
Shah, Zubair ;
Shah, Nilay ;
Needleman, Bradley ;
Mikami, Dean ;
Narula, Vimal ;
Perry, Kyle ;
Hazey, Jeffrey ;
Kampfrath, Thomas ;
Kollengode, Madhukar ;
Sun, Qinghua ;
Satoskar, Abhay R. ;
Lumeng, Carey ;
Moffatt-Bruce, Susan ;
Rajagopalan, Sanjay .
PLOS ONE, 2011, 6 (01)
[40]   Precursors for Nonlymphoid-Tissue Treg Cells Reside in Secondary Lymphoid Organs and Are Programmed by the Transcription Factor BATF [J].
Delacher, Michael ;
Imbusch, Charles D. ;
Hotz-Wagenblatt, Agnes ;
Mallm, Jan-Philipp ;
Bauer, Katharina ;
Simon, Malte ;
Riegel, Dania ;
Rendeiro, Andre F. ;
Bittner, Sebastian ;
Sanderink, Lieke ;
Pant, Asmita ;
Schmidleithner, Lisa ;
Braband, Kathrin L. ;
Echtenachter, Bernd ;
Fischer, Alexander ;
Giunchiglia, Valentina ;
Hoffmann, Petra ;
Edinger, Matthias ;
Bock, Christoph ;
Rehli, Michael ;
Brors, Benedikt ;
Schmidl, Christian ;
Feuerer, Markus .
IMMUNITY, 2020, 52 (02) :295-+