Rationale for LDH-targeted cancer immunotherapy.

Eur J Cancer

Laboratoire de Recherche Translationnelle en Immunothérapie (LRTI), INSERM U1015, Gustave Roussy, Villejuif, France; Département d'Innovation Thérapeutique et d'Essais Précoces (DITEP), Gustave Roussy, 94805 Villejuif, France; Centre d'Investigation Clinique BIOTHERIS, INSERM CIC1428, Gustave Roussy, Villejuif, France; Faculté de Médecine, Université Paris-Saclay, Le Kremlin-Bicêtre, France. Electronic address:

Published: March 2023

Immunotherapies have significantly improved the survival of patients in many cancers over the last decade. However, primary and secondary resistances are encountered in most patients. Unravelling resistance mechanisms to cancer immunotherapies is an area of active investigation. Elevated levels of circulating enzyme lactate dehydrogenase (LDH) have been historically considered in oncology as a marker of bad prognosis, usually attributed to elevated tumour burden and cancer metabolism. Recent evidence suggests that elevated LDH levels could be independent from tumour burden and contain a negative predictive value, which could help in guiding treatment strategies in immuno-oncology. In this review, we decipher the rationale supporting the potential of LDH-targeted therapeutic strategies to tackle the direct immunosuppressive effects of LDH on a wide range of immune cells, and enhance the survival of patients treated with cancer immunotherapies.

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http://dx.doi.org/10.1016/j.ejca.2022.11.032DOI Listing

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