Metabolic profiles of regulatory T cells and their adaptations to the tumor microenvironment: implications for antitumor immunity

Abstract

Characterized by the expression of the critical transcription factor forkhead box protein P3, regulatory T (Treg) cells are an essential part of the immune system, with a dual effect on the pathogenesis of autoimmune diseases and cancer. Targeting Tregs to reestablish the proinflammatory and immunogenic tumor microenvironment (TME) is an increasingly attractive strategy for cancer treatment and has been emphasized in recent years. However, attempts have been significantly hindered by the subsequent autoimmunity after Treg ablation owing to systemic loss of their suppressive capacity. Cellular metabolic reprogramming is acknowledged as a hallmark of cancer, and emerging evidence suggests that elucidating the underlying mechanisms of how intratumoral Tregs acquire metabolic fitness and superior immunosuppression in the TME may contribute to clinical benefits. In this review, we discuss the common and distinct metabolic profiles of Tregs in peripheral tissues and the TME, as well as the differences between Tregs and other conventional T cells in their metabolic preferences. By focusing on the critical roles of different metabolic programs, such as glycolysis, oxidative phosphorylation, fatty acid oxidation, fatty acid synthesis, and amino acid metabolism, as well as their essential regulators in modulating Treg proliferation, migration, and function, we hope to provide new insights into Treg cell-targeted antitumor immunotherapies.

Integrating single-cell RNA-seq and bulk RNA-seq to construct prognostic signatures to explore the role of glutamine metabolism in breast cancer

“…Immunotherapy of BC has proved to be a challenge in the era of personalized treatment. The interaction between cancer cells and the immune system is a complex, dynamic, and constantly changing process (36). Unlike targeted therapy and endocrine therapy, which effectively guide attacks by identifying targets with biological markers, there are no therapeutic markers for immunotherapy.…”

Establishment and experimental validation of a novel cuproptosis-related gene signature for prognostic implication in cholangiocarcinoma

“…Immune cell infiltration was compared between the low-risk and high-risk groups, and the level of immune cell infiltration, including macrophages and Tregs, was found to be elevated in the high-risk group compared to the low-risk group. An increase in tumor-associated macrophages and Treg cells can create a suppressive immune microenvironment that is associated with poor patient prognosis ( 29 – 31 ). Treg infiltration was increased in tumor tissues of patients with CCA, suggesting that it may be related to the development of CCA ( 32 ).…”

Recent advances in ocular graft-versus-host disease

“…Recently, in a prospective clinical trial, 28 eyes with refractory GVHD–DED exhibited substantial relief after treatment with exosomes from MSCs, showing reduced fluorescein scores, longer tear breakup time, increased tear secretion, and lower OSDI scores ( 130 ). Regulatory T cells (Tregs) have a critical role in the immune system by maintaining immune homeostasis and preventing the occurrence of autoimmune diseases ( 131 , 132 ). It has been demonstrated that early post-transplantation treatment of patients with expanded Tregs + BETi (a bromodomain and extraterminal protein inhibitor) improved the level of Tregs and exhibit a significant diminution of GVHD clinical scores with less ocular involvement ( 133 ).…”