Emerging Role of Extracellular pH in Tumor Microenvironment as a Therapeutic Target for Cancer Immunotherapy

Cells, Journal Year: 2024, Volume and Issue: 13(22), P. 1924 - 1924

Published: Nov. 20, 2024

Identifying definitive biomarkers that predict clinical response and resistance to immunotherapy remains a critical challenge. One emerging factor is extracellular acidosis in the tumor microenvironment (TME), which significantly impairs immune cell function contributes failure. However, acidic conditions TME disrupt interaction between cancer cells, driving tumor-infiltrating T cells NK into an inactivated, anergic state. Simultaneously, promotes recruitment activation of immunosuppressive such as myeloid-derived suppressor regulatory (Tregs). Notably, acidity enhances exosome release from Tregs, further amplifying immunosuppression. Tumor thus acts "protective shield," neutralizing anti-tumor responses transforming pro-tumor allies. Therefore, targeting lactate metabolism has emerged promising strategy overcome this barrier, with approaches including buffer agents neutralize pH inhibitors block production or transport, thereby restoring efficacy TME. Recent discoveries have identified genes involved (pHe) regulation, presenting new therapeutic targets. Moreover, ongoing research aims elucidate molecular mechanisms acidification develop treatments modulate levels enhance outcomes. Additionally, future studies are crucial validate safety pHe-targeted therapies patients. Thus, review explores regulation pHe its potential role improving immunotherapy.

Language: Английский

Targeting Lactate: An Emerging Strategy for Macrophage Regulation in Chronic Inflammation and Cancer

Biomolecules, Journal Year: 2024, Volume and Issue: 14(10), P. 1202 - 1202

Published: Sept. 24, 2024

Lactate accumulation and macrophage infiltration are pivotal features of both chronic inflammation cancer. Lactate, once regarded merely as an aftereffect glucose metabolism, is now gaining recognition for its burgeoning spectrum biological roles immunomodulatory significance. Recent studies have evidenced that macrophages display divergent immunophenotypes in different diseases, which play a role disease management by modulating polarization within the microenvironment. The specific patterns high-lactate environment their contribution to progression cancer remain contentious. This review presents current evidence on crosstalk lactate Additionally, we provide in-depth exploration yet enigmatic mechanisms through orchestrates pathogenesis, thereby offering novel perspectives development targeted therapeutic interventions

Language: Английский