Faculté de Médecine, Université de Genève, Genève, Switzerland; Laboratoire de Recherche Translationnelle en Immunothérapie (LRTI), INSERM U1015, Gustave Roussy, Villejuif, France.
Laboratoire de Recherche Translationnelle en Immunothérapie (LRTI), INSERM U1015, Gustave Roussy, Villejuif, France; INSERM UMR 1163, Imagine Institute, Université de Paris, F-75015 Paris, France.
Eur J Cancer. 2023 Mar;181:166-178. doi: 10.1016/j.ejca.2022.11.032. Epub 2022 Dec 14.
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.
在过去的十年中，免疫疗法显著提高了许多癌症患者的生存率。然而，大多数患者都会出现原发性和继发性耐药。揭示癌症免疫疗法耐药的机制是一个活跃的研究领域。在肿瘤学中，循环酶乳酸脱氢酶（LDH）水平升高一直被认为是预后不良的标志物，通常归因于肿瘤负荷增加和癌症代谢。最近的证据表明，LDH 水平升高可能与肿瘤负荷无关，并且具有负预测价值，这有助于指导免疫肿瘤学中的治疗策略。在这篇综述中，我们阐明了支持针对 LDH 的治疗策略的基本原理，这些策略旨在解决 LDH 对广泛的免疫细胞的直接免疫抑制作用，并提高接受癌症免疫疗法治疗的患者的生存率。
