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

来源：

ONCOGENE | 2025年 / 44卷 / 25期

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

页码：2011 / 2024

页数：14

共 219 条

[1] Differential PI3Kδ Signaling in CD4+ T-cell Subsets Enables Selective Targeting of T Regulatory Cells to Enhance Cancer Immunotherapy [J].

Ahmad, Shamim ;

Abu-Eid, Rasha ;

Shrimali, Rajeev ;

Webb, Mason ;

Verma, Vivek ;

Doroodchi, Atbin ;

Berrong, Zuzana ;

Samara, Raed ;

Rodriguez, Paulo C. ;

Mkrtichyan, Mikayel ;

Khleif, Samir N. .

CANCER RESEARCH, 2017, 77 (08) :1892-1904

[2] Tumor-infiltrating human CD4+ regulatory T cells display a distinct TCR repertoire and exhibit tumor and neoantigen reactivity [J].

Ahmadzadeh, Mojgan ;

Pasetto, Anna ;

Jia, Li ;

Deniger, Drew C. ;

Stevanovic, Sanja ;

Robbins, Paul F. ;

Rosenberg, Steven A. .

SCIENCE IMMUNOLOGY, 2019, 4 (31)

[3] Inactivation of PI(3)K p110δ breaks regulatory T-cell-mediated immune tolerance to cancer [J].

Ali, Khaled ;

Soond, Dalya R. ;

Pineiro, Roberto ;

Hagemann, Thorsten ;

Pearce, Wayne ;

Lim, Ee Lyn ;

Bouabe, Hicham ;

Scudamore, Cheryl L. ;

Hancox, Timothy ;

Maecker, Heather ;

Friedman, Lori ;

Turner, Martin ;

Okkenhaug, Klaus ;

Vanhaesebroeck, Bart .

NATURE, 2014, 510 (7505) :407-+

[4] Regulatory T Cells in Skin Facilitate Epithelial Stem Cell Differentiation [J].

Ali, Niwa ;

Zirak, Bahar ;

Rodriguez, Robert Sanchez ;

Pauli, Mariela L. ;

Hong-An Truong ;

Lai, Kevin ;

Ahn, Richard ;

Corbin, Kaitlin ;

Lowe, Margaret M. ;

Scharschmidt, Tiffany C. ;

Taravati, Keyon ;

Tan, Madeleine R. ;

Ricardo-Gonzalez, Roberto R. ;

Nosbaum, Audrey ;

Bertolini, Marta ;

Liao, Wilson ;

Nestle, Frank O. ;

Paus, Ralf ;

Cotsarelis, George ;

Abbas, Abul K. ;

Rosenblum, Michael D. .

CELL, 2017, 169 (06) :1119-+

[5] The ectonucleotidases CD39 and CD73: Novel checkpoint inhibitor targets [J].

Allard, Bertrand ;

Longhi, Maria Serena ;

Robson, Simon C. ;

Stagg, John .

IMMUNOLOGICAL REVIEWS, 2017, 276 (01) :121-144

[6] Foxp3 Reprograms T Cell Metabolism to Function in Low-Glucose, High-Lactate Environments [J].

Angelin, Alessia ;

Gil-de-Gomez, Luis ;

Dahiya, Satinder ;

Jiao, Jing ;

Guo, Lili ;

Levine, Matthew H. ;

Wang, Zhonglin ;

Quinn, William J., III ;

Kopinski, Piotr K. ;

Wang, Liqing ;

Akimova, Tatiana ;

Liu, Yujie ;

Bhatti, Tricia R. ;

Han, Rongxiang ;

Laskin, Benjamin L. ;

Baur, Joseph A. ;

Blair, Ian A. ;

Wallace, Douglas C. ;

Hancock, Wayne W. ;

Beier, Ulf H. .

CELL METABOLISM, 2017, 25 (06) :1282-+

[7] SCENITH: A Flow Cytometry-Based Method to Functionally Profile Energy Metabolism with Single-Cell Resolution [J].

Arguello, Rafael J. ;

Combes, Alexis J. ;

Char, Remy ;

Gigan, Julien-Paul ;

Baaziz, Ania I. ;

Bousiquot, Evens ;

Camosseto, Voahirana ;

Samad, Bushra ;

Tsui, Jessica ;

Yan, Peter ;

Boissonneau, Sebastien ;

Figarella-Branger, Dominique ;

Gatti, Evelina ;

Tabouret, Emeline ;

Krummel, Matthew F. ;

Pierre, Philippe .

CELL METABOLISM, 2020, 32 (06) :1063-1075.e7

[8] Metabolic programming and immune suppression in the tumor microenvironment [J].

Arner, Emily N. ;

Rathmell, Jeffrey C. .

CANCER CELL, 2023, 41 (03) :421-433

[9] Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation [J].

Arpaia, Nicholas ;

Campbell, Clarissa ;

Fan, Xiying ;

Dikiy, Stanislav ;

van der Veeken, Joris ;

deRoos, Paul ;

Liu, Hui ;

Cross, Justin R. ;

Pfeffer, Klaus ;

Coffer, Paul J. ;

Rudensky, Alexander Y. .

NATURE, 2013, 504 (7480) :451-+

[10] CXCR3 expression in regulatory T cells drives interactions with type I dendritic cells in tumors to restrict CD8+T cell antitumor immunity [J].

Ayala, Mariela A. Moreno ;

Campbell, Timothy F. ;

Zhang, Chenyu ;

Dahan, Noa ;

Bockman, Alissa ;

Prakash, Varsha ;

Feng, Lawrence ;

Sher, Theo ;

DuPage, Michel .

IMMUNITY, 2023, 56 (07) :1613-+

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