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Blocking inflammation to improve immunotherapy of advanced cancer.
Immunology ( IF 4.9 ) Pub Date : 2019-12-27 , DOI: 10.1111/imm.13164 Antonio Macciò 1 , Clelia Madeddu 2
Immunology ( IF 4.9 ) Pub Date : 2019-12-27 , DOI: 10.1111/imm.13164 Antonio Macciò 1 , Clelia Madeddu 2
Affiliation
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The ability to induce functional reprogramming of regulatory T (Treg) cells in the tumor microenvironment is an extremely important therapeutic opportunity. However, when discussing such an approach, the opposing effect that the activation of the Treg cell compartments may have in inducing the immune inflammatory response and its link with the efficacy of immunotherapy should be considered. In fact, Treg reprogramming has a dual effect: immediate, with mechanisms that activate immunosurveillance, and late, mediated by the macrophage activation that yields an inflammatory status that is deleterious for the antineoplastic efficiency of the immune system response. Persistence of the inflammatory response is associated with specific changes of oxidative and glycolytic metabolic pathways that interfere with conventional T‐cell activation and function and may be one of the reasons for the failure of immunotherapy in advanced cancer patients. Therefore, in addition to modulating Treg cell action, the combined use of drugs able to block chronic inflammation mediated mainly by macrophages, to counteract the oxidative stress, and to positively regulate the metabolic derangements, could improve the effectiveness of modern immunotherapy. In conclusion, reprogramming of Treg cells may be an appropriate strategy for treating early stages of neoplastic diseases, whereas other immunosuppressive mechanisms should be the target of a combined immunotherapy approach in more advanced phases of cancer.
中文翻译：
阻断炎症以改善晚期癌症的免疫疗法。
在肿瘤微环境中诱导调节性T（Treg）细胞功能性重编程的能力是极其重要的治疗机会。但是，在讨论这种方法时，应考虑Treg细胞区隔的激活在诱导免疫炎症反应中的相反作用及其与免疫疗法功效的联系。实际上，Treg重编程具有双重作用：即时的，具有激活免疫监视的机制，后期的，由巨噬细胞激活介导的，其产生的炎症状态对免疫系统反应的抗肿瘤效率有害。炎症反应的持续存在与氧化和糖酵解代谢途径的特定改变有关，这些改变干扰了传统的T细胞活化和功能，可能是晚期癌症患者免疫治疗失败的原因之一。因此，除了调节Treg细胞的作用外，结合使用能够阻断主要由巨噬细胞介导的慢性炎症，抵消氧化应激并积极调节代谢紊乱的药物，可以提高现代免疫疗法的有效性。总之，Treg细胞的重编程可能是治疗肿瘤性疾病早期阶段的合适策略，而其他免疫抑制机制应成为癌症更晚期阶段联合免疫疗法的目标。
更新日期：2020-03-26
中文翻译：
阻断炎症以改善晚期癌症的免疫疗法。
在肿瘤微环境中诱导调节性T（Treg）细胞功能性重编程的能力是极其重要的治疗机会。但是，在讨论这种方法时，应考虑Treg细胞区隔的激活在诱导免疫炎症反应中的相反作用及其与免疫疗法功效的联系。实际上，Treg重编程具有双重作用：即时的，具有激活免疫监视的机制，后期的，由巨噬细胞激活介导的，其产生的炎症状态对免疫系统反应的抗肿瘤效率有害。炎症反应的持续存在与氧化和糖酵解代谢途径的特定改变有关，这些改变干扰了传统的T细胞活化和功能，可能是晚期癌症患者免疫治疗失败的原因之一。因此，除了调节Treg细胞的作用外，结合使用能够阻断主要由巨噬细胞介导的慢性炎症，抵消氧化应激并积极调节代谢紊乱的药物，可以提高现代免疫疗法的有效性。总之，Treg细胞的重编程可能是治疗肿瘤性疾病早期阶段的合适策略，而其他免疫抑制机制应成为癌症更晚期阶段联合免疫疗法的目标。
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