Role of Monocarboxylate Transporters in Cancer Immunology and Their Therapeutic Potential Publisher Pubmed



F Faghihkhorasani FERDOS ; M Moosavi MONA ; NULL ; M Kavei MOHAMMED ; S Karimi SOROUSH ; M Seyed Karimi MAHSHID ; P Vezvaei PAYAM ; M Manafi Varkiani MAHSA ; Ar Aref Amir REZA ; N Ebrahimi NASIM
Source: British Journal of Pharmacology Published:2025

Abstract

Monocarboxylate transporters (MCTs) affect cancer metabolism and the regulation of immune responses, making them targets for cancer therapy. This study examines the roles of MCTs, specifically MCT1 and MCT4, in various cancer types and their influence on the advancement of tumours, metastasis and patient prognosis. We analyse the interaction among MCTs, tumour microenvironments (TMEs) and the immune system, as biomarkers and targets for therapy. Initial clinical trials have demonstrated encouraging outcomes with MCT inhibitors, including AZD3965. The combination of MCT inhibition and immunotherapy, such as immune checkpoint blockade, has shown synergistic effects in boosting the antitumour responses of the body's immune system. This study reviews the importance of MCTs and their potential as new targets for enhancing cancer therapy efficacy, especially when used in conjunction with current medicine treatment regimes. In numerous malignancies, tumour cells form a metabolic symbiosis wherein glycolytic cells, marked by elevated MCT4 expression, secrete lactate into the TME, while oxidative cancer cells, expressing MCT1, absorb this lactate as a metabolic substrate for the tricarboxylic acid cycle. Disrupting this lactate shuttle through targeted inhibition of MCTs is a promising strategy to overcome immune evasion and enhance the efficacy of immunotherapies. Targeting monocarboxylate transporters (MCTs) in glycolytic and oxidative tumour cells enhances antitumour immunity. Combinational therapy using MCT1 inhibitors (e.g. AZD3965), MCT4 inhibitors and immune checkpoint blockade can suppress lactate-mediated immunosuppression in the TME. By disrupting lactate shuttling between glycolytic and oxidative tumour cells, this strategy promotes T cell function and improves cancer treatment outcomes. © 2025 Elsevier B.V., All rights reserved.