PD-L1 checkpoint blockade promotes regulatory T cell activity that underlies therapy resistance DOI Open Access
Mandy van Gulijk, Anneloes van Krimpen, Sjoerd Schetters

et al.

Science Immunology, Journal Year: 2023, Volume and Issue: 8(83)

Published: May 19, 2023

Despite the clinical success of immune checkpoint blockade (ICB), in certain cancer types, most patients with do not respond well. Furthermore, for whom ICB is initially successful, this often short-lived because development resistance to ICB. The mechanisms underlying primary or secondary are incompletely understood. Here, we identified preferential activation and enhanced suppressive capacity regulatory T cells (Treg cells) αPD-L1 therapy-resistant solid tumor-bearing mice. Treg cell depletion reversed concomitant expansion effector cells. Moreover, found that tumor-infiltrating human skin cancer, non-small lung up-regulated a transcriptional gene program after treatment, which correlated lack treatment response. αPD-1/PD-L1-induced PD-1+ was also seen peripheral blood mesothelioma, especially nonresponders. Together, these data reveal αPD-1 unleashes immunosuppressive role cells, resulting therapy resistance, suggesting targeting an important adjunct strategy enhance therapeutic efficacy.

Language: Английский

Lactic acid promotes PD-1 expression in regulatory T cells in highly glycolytic tumor microenvironments DOI Creative Commons
Shogo Kumagai, Shohei Koyama, Kota Itahashi

et al.

Cancer Cell, Journal Year: 2022, Volume and Issue: 40(2), P. 201 - 218.e9

Published: Jan. 28, 2022

Language: Английский

Citations

522
Small molecule metabolites: discovery of biomarkers and therapeutic targets DOI Creative Commons
Shi Qiu, Ying Cai, Hong Yao

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: March 20, 2023

Metabolic abnormalities lead to the dysfunction of metabolic pathways and metabolite accumulation or deficiency which is well-recognized hallmarks diseases. Metabolite signatures that have close proximity subject's phenotypic informative dimension, are useful for predicting diagnosis prognosis diseases as well monitoring treatments. The lack early biomarkers could poor serious outcomes. Therefore, noninvasive methods with high specificity selectivity desperately needed. Small molecule metabolites-based metabolomics has become a specialized tool biomarker pathway analysis, revealing possible mechanisms human various deciphering therapeutic potentials. It help identify functional related variation delineate biochemical changes indicators pathological damage prior disease development. Recently, scientists established large number profiles reveal underlying networks target exploration in biomedicine. This review summarized analysis on potential value small-molecule candidate metabolites clinical events, may better diagnosis, prognosis, drug screening treatment. We also discuss challenges need be addressed fuel next wave breakthroughs.

Language: Английский

Citations

382
Turning cold tumors hot: from molecular mechanisms to clinical applications DOI
Jiahui Zhang, Di Huang, Phei Er Saw

et al.

Trends in Immunology, Journal Year: 2022, Volume and Issue: 43(7), P. 523 - 545

Published: May 25, 2022

Language: Английский

Citations

324
Tumor-infiltrating regulatory T cells as targets of cancer immunotherapy DOI Creative Commons

Christopher Tay,

Atsushi Tanaka, Shimon Sakaguchi

et al.

Cancer Cell, Journal Year: 2023, Volume and Issue: 41(3), P. 450 - 465

Published: March 1, 2023

Language: Английский

Citations

265
The role of lipids in cancer progression and metastasis DOI Creative Commons
Miguel Martín‐Pérez,

Uxue Urdiroz-Urricelqui,

Claudia Bigas

et al.

Cell Metabolism, Journal Year: 2022, Volume and Issue: 34(11), P. 1675 - 1699

Published: Oct. 18, 2022

Language: Английский

Citations

258
Mechanisms of regulatory T cell infiltration in tumors: implications for innovative immune precision therapies DOI Creative Commons
Shohei Koyama, Hiroyoshi Nishikawa

Journal for ImmunoTherapy of Cancer, Journal Year: 2021, Volume and Issue: 9(7), P. e002591 - e002591

Published: July 1, 2021

With the broad application of cancer immunotherapies such as immune checkpoint inhibitors in multiple types, immunological landscape tumor microenvironment (TME) has become enormously important for determining optimal treatment. Tumors can be immunologically divided into two categories: inflamed and non-inflamed based on extent cell infiltration their activation status. In general, are preferable tumors than tumors. Regulatory T cells (Tregs), an immunosuppressive subset CD4 + cells, play essential role maintaining self-tolerance homeostasis. immunity, Tregs compromise surveillance against healthy individuals impair antitumor response tumor-bearing hosts. Tregs, therefore, accelerate evasion by leading to development progression various types cancer. Therefore, considered a crucial therapeutic target immunotherapy. Abundant observed TME many cancer, both Diverse mechanisms Treg accumulation, activation, survival have been uncovered different indicating importance understanding mechanism each patient when selecting Treg-targeted therapy. Here, we review recent advances abundance optimize Furthermore, addition conventional strategies targeting surface molecules predominantly expressed reagents signaling pathways specifically employed infiltration, type illustrated novel therapies. The effectiveness precision therapy depends conditions patient.

Language: Английский

Citations

223
Metabolic adaptation of lymphocytes in immunity and disease DOI Creative Commons
Nicole M. Chapman, Hongbo Chi

Immunity, Journal Year: 2022, Volume and Issue: 55(1), P. 14 - 30

Published: Jan. 1, 2022

Adaptive immune responses mediated by T cells and B are crucial for protective immunity against pathogens tumors. Differentiation function of require dynamic reprogramming cellular metabolism. Metabolic inputs, pathways, enzymes display remarkable flexibility heterogeneity, especially in vivo. How metabolic plasticity adaptation dictate functional specialization is fundamental to our understanding therapeutic modulation the system. Extensive progress has been made characterizing effects networks on cell fate discrete microenvironments or immunological contexts. In this review, we summarize how rewiring metabolism determines outcome adaptive vivo, with a focus metabolites, nutrients, driver genes immunometabolism instruct programming during infection, inflammation, cancer mice humans. Understanding context-dependent remodeling will manifest legitimate opportunities intervention human disease.

Language: Английский

Citations

187
Metabolic communication in the tumour–immune microenvironment DOI
Kung‐Chi Kao,

Stefania Vilbois,

Chin‐Hsien Tsai

et al.

Nature Cell Biology, Journal Year: 2022, Volume and Issue: 24(11), P. 1574 - 1583

Published: Oct. 13, 2022

Language: Английский

Citations

185
Tumor resistance to ferroptosis driven by Stearoyl-CoA Desaturase-1 (SCD1) in cancer cells and Fatty Acid Biding Protein-4 (FABP4) in tumor microenvironment promote tumor recurrence DOI Creative Commons
Géraldine Luis, Adrien Godfroid, Shin Nishiumi

et al.

Redox Biology, Journal Year: 2021, Volume and Issue: 43, P. 102006 - 102006

Published: May 14, 2021

Tumor recurrence is a major clinical issue that represents the principal cause of cancer-related deaths, with few targetable common pathways. Mechanisms by which residual tumors persist and progress under continuous shift between hypoxia-reoxygenation after neoadjuvent-therapy are unknown. In this study, we investigated role lipid metabolism tumor redox balance in recurrence. Lipidomics, proteomics mass spectrometry imaging approaches where applied to mouse models Genetic pharmacological inhibitions mediators were used vivo functional assays vitro. We found stearoyl-CoA desaturase-1 (SCD1) expressed cancer cells fatty acid binding protein-4 (FABP4) produced endothelial (TECs) adipocytes microenvironment (TME) essential for relapse response tyrosine kinase inhibitors (TKI) chemotherapy. SCD1 FABP4 also upregulated recurrent human breast samples correlated worse prognosis patients different types tumors. Mechanistically, leads (FA) desaturation derived from TEM enhances droplet (LD) cells, cooperatively protect oxidative stress-induced ferroptosis. revealed mobilization elicit intrinsic antioxidant anti-ferroptotic resources survival regrowth harsh TME. Inhibition transport TME inhibitor reduced genetic — or targeting vivo, was abolished completely. This finding unveils it worth taking advantage addiction, as vulnerability design novel treatment strategy prevent

Language: Английский

Citations

183
CD8+ T cells in the cancer-immunity cycle DOI Creative Commons
Josephine R. Giles, Anna-Maria Globig,

Susan M. Kaech

et al.

Immunity, Journal Year: 2023, Volume and Issue: 56(10), P. 2231 - 2253

Published: Oct. 1, 2023

Language: Английский

Citations

171