Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran; Immunology Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran.
Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran; Department of Laboratory Sciences, Khomein University of Medical Sciences, Khomein, Iran.
Int Immunopharmacol. 2021 May;94:107461. doi: 10.1016/j.intimp.2021.107461. Epub 2021 Feb 13.
Recent advances in cancer immunotherapy have raised hopes for treating cancers that are resistant to conventional therapies. Among the various immunotherapy methods, the immune checkpoint (IC) blockers were more promising and have paved their way to the clinic. Tumor cells induce the expression of ICs on the immune cells and derive them to a hyporesponsive exhausted phenotype. IC blockers could hinder immune exhaustion in the tumor microenvironment and reinvigorate immune cells for an efficient antitumor response. Despite the primary success of IC blockers in the clinic, the growing numbers of refractory cases require an in-depth study of the cellular and molecular mechanisms underlying IC expression and function. Immunometabolism is recently found to be a key factor in the regulation of immune responses. Activated or exhausted immune cells exploit different metabolic pathways. Tumor cells can suppress antitumor responses via immunometabolism alteration. Therefore, it is expected that concurrent targeting of ICs and immunometabolism pathways can cause immune cells to restore their antitumor activity. In this review, we dissected the reciprocal interactions of immune cell metabolism with expression and signaling of ICs in the tumor microenvironment. Recent findings on dual targeting of ICs and metabolic checkpoints have also been discussed.
近年来，癌症免疫疗法的进展为治疗对传统疗法耐药的癌症带来了新的希望。在各种免疫疗法中，免疫检查点（IC）抑制剂更有前景，并已进入临床应用。肿瘤细胞在免疫细胞上诱导表达 IC，并将其诱导为低反应性耗竭表型。IC 抑制剂可以阻止肿瘤微环境中的免疫耗竭，使免疫细胞重新激活，产生有效的抗肿瘤反应。尽管 IC 抑制剂在临床上取得了初步成功，但越来越多的难治性病例需要深入研究 IC 表达和功能的细胞和分子机制。免疫代谢最近被发现是调节免疫反应的关键因素。激活或耗竭的免疫细胞利用不同的代谢途径。肿瘤细胞可以通过免疫代谢改变来抑制抗肿瘤反应。因此，预计同时靶向 IC 和免疫代谢途径可以使免疫细胞恢复其抗肿瘤活性。在这篇综述中，我们剖析了免疫细胞代谢与肿瘤微环境中 IC 表达和信号之间的相互作用。还讨论了 IC 和代谢检查点的双重靶向的最新发现。
