Acidosis as a metabolic barrier to immunotherapy: mechanisms and therapeutic opportunities
Year: 2026
Type: article
Abstract: Immune evasion remains a major obstacle to cancer immunotherapy and arises from multifaceted mechanisms. Among these, the acidic tumor microenvironment (TME) constitutes a critical physicochemical barrier that orchestrates immunosuppression. In this narrative review, we summarize the principal mechanisms through which TME acidosis remodels the immune landscape. Acidosis impairs the immunosurveillance and cytotoxic functions of innate and adaptive effector cells while promoting the expansion and suppressive potency of regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). Preclinical studies indicate that targeting tumor acidosis can partially restore antitumor immune function and may mitigate resistance to immunotherapy. These findings support biological plausibility, but they derive primarily from in vitro systems and murine models, corroborated by in silico analyses. Clinical evidence, however, remains limited to early-phase safety and target-engagement studies, and translation to patients is therefore not yet established. We further consider pH imaging as an emerging translational tool for patient selection and pharmacodynamic monitoring of pH-directed interventions. Targeting metabolic acidity is a biologically plausible and preclinically supported strategy that warrants rigorous clinical evaluation, ideally guided by non-invasive assessment of tumor pH. Clinical trial number : Not applicable.
Source: Cellular Oncology
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,390
OpenAlex ID: W7223454698
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