Metabolic crosstalk between tumors and regulatory immune cells

The tumor microenvironment (TME) is a metabolically dynamic niche where cancer cells and immune cells interact to influence tumor progression and immune evasion. Tumor cells reprogram metabolism-enhancing glycolysis, glutamine use, and lipid pathways—to survive under nutrient-limited, hypoxic conditions. Regulatory immune cells, including Tregs and Bregs, adapt their metabolism to maintain suppressive function within the TME, often relying on oxidative phosphorylation and fatty acid oxidation. Tumor-derived metabolites, such as lactate and adenosine, further reinforce their immunosuppressive activity. Understanding this bidirectional metabolic crosstalk is critical for identifying therapeutic strategies to disrupt immune suppression and enhance antitumor immunity.Despite advances in cancer immunotherapy, many tumors evade immune destruction by exploiting regulatory immune cells, such as Tregs and Bregs, which suppress effector T and NK cell activity. A key mechanism driving this immune evasion is metabolic crosstalk: tumors create a nutrient-depleted, hypoxic, and metabolite-rich microenvironment that reinforces the suppressive function and survival of regulatory immune cells. While immunotherapies targeting checkpoint pathways have shown promise, they often fail in tumors with abundant regulatory cells, highlighting a critical gap in therapeutic strategies.Recent studies indicate that targeting metabolic pathways—such as oxidative phosphorylation, fatty acid oxidation, or NAD⁺-dependent signaling—can modulate regulatory cell function and reprogram the tumor microenvironment. Our goal is to dissect how tumor-derived metabolites influence Breg and Treg metabolism and identify actionable metabolic checkpoints. By combining metabolomic profiling, functional assays, and targeted interventions, this research aims to uncover novel strategies to disrupt tumor–immune metabolic crosstalk and enhance antitumor immunity.This Research Topic focuses on the metabolic interactions between tumors and regulatory immune cells that shape the tumor microenvironment and influence cancer progression. We invite contributions that explore mechanistic insights, translational potential, and therapeutic strategies. Specific themes include:• Tumor-driven metabolic reprogramming: How cancer cells alter nutrient availability, oxygen levels, and metabolite production to influence immune cell function.• Metabolism of regulatory immune cells: Energy pathways (glycolysis, oxidative phosphorylation, fatty acid oxidation), NAD⁺/sirtuin signaling, and other metabolic programs that sustain Tregs and Bregs in the TME.• Tumor–immune metabolic crosstalk: Bidirectional interactions between tumor metabolites (e.g., lactate, adenosine) and immune cell metabolism.• Therapeutic targeting of metabolic pathways: Strategies to modulate regulatory cell metabolism, reprogram the TME, and enhance immunotherapy efficacy.• Emerging technologies and approaches: Single-cell metabolomics, metabolic imaging, and functional assays to dissect tumor–immune interactions.• Clinical implications and translational studies: Preclinical or clinical evidence linking metabolic crosstalk to patient outcomes.Please note that manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this Research Topic. Topic editors: Alak Manna, Shaoquan Zheng Source: https://www.frontiersin.org/research-topics/76286/metabolic-crosstalk-between-tumors-and-regulatory-immune-cells