Uncovering the interplay between pH receptors and immune cells: Potential drug targets (Review)

作者：Lin Cao, Tianqiao Huang, Xiaohong Chen, Weisha Li, Xingjiu Yang, Wenlong Zhang, Mengyuan Li, Ran Gao · 发表于：Oncology Reports · 年份：2021 · DOI：10.3892/or.2021.8179 · 被引用次数：18 · 研究领域：Bioactive Compounds and Antitumor Agents、ATP Synthase and ATPases Research、Adenosine and Purinergic Signaling

Extracellular acidosis is associated with various immunopathological states. The microenvironment of numerous solid tumours and inflammatory responses during acute or chronic infection are all related to a pH range of 5.5‑7.0. The relationship between inflammation and immune escape, cancer metabolism, and immunologic suppression drives researchers to focus on the effects of low pH on diverse components of disease immune monitoring. The potential effect of low extracellular pH on the immune function reveals the importance of pH in inflammatory and immunoreactive processes. In this review, the mechanism of how pH receptors, including monocarboxylate transporters (MCTs), Na + /H + exchanger 1, carbonic anhydrases (CAs), vacuolar‑ATPase, and proton‑sensing G‑protein coupled receptors (GPCRs), modulate the immune system in disease, especially in cancer, were studied. Their role in immunocyte growth and signal transduction as part of the immune response, as well as cytokine production, have been documented in great detail. Currently, immunotherapy strategies have positive therapeutic effects for patients. However, the acidic microenvironment may block the effect of immunotherapy through compensatory feedback mechanisms, leading to drug resistance. Therefore, we highlight promising therapeutic developments regarding pH manipulation and provide a framework for future research.