Rationale for LDH-targeted cancer immunotherapy

Immunotherapies have significantly improved the survival of patients in many can-cers 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.(c) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Automated summary

Immunotherapies have improved cancer patients' survival, but many encounter primary and secondary resistances. Investigating resistance mechanisms to cancer immunotherapies is an active area of research. Recent evidence suggests that elevated levels of LDH may have negative predictive value independent of tumor burden and guide treatment strategies in immuno-oncology. This review explores the potential of LDH-targeted therapeutic strategies to overcome the immunosuppressive effects of LDH and enhance patient survival with cancer immunotherapies.