Rationale for LDH-targeted cancer immunotherapy

Eur J Cancer. 2023 Mar:181:166-178. doi: 10.1016/j.ejca.2022.11.032. Epub 2022 Dec 14.

Abstract

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.

Keywords: Cancer; Immunosuppression; Immunotherapy; Lactate dehydrogenase (LDH).

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Immunotherapy*
  • L-Lactate Dehydrogenase* / metabolism
  • Neoplasms* / metabolism
  • Neoplasms* / therapy
  • Prognosis

Substances

  • L-Lactate Dehydrogenase