Khalil Rehab G, Mohammed Dina A, Hamdalla Hadeer M, Ahmed Osama M
Immunology Division, Department of Zoology, Faculty of Science, Beni-Suef University, P.O. Box 62521, Beni-Suef, Egypt.
Department of Zoology, Faculty of Science, Beni-Suef University, P.O. Box 62521, Beni-Suef, Egypt.
Cytokine. 2025 Feb;186:156834. doi: 10.1016/j.cyto.2024.156834. Epub 2024 Dec 17.
T lymphocytes are among the immunological cells that make up the tumor microenvironment (TME), and they are essential in the growth of tumors and anti-tumor reactions. Regulatory T cells (Treg cells) are a subset of CD4+ T cells in the immune system that suppress the immune system. They are distinguished by their expression of the master transcription factor forkhead box protein P3 (FOXP3). Furthermore, Treg cells are essential for maintaining immunological homeostasis, inhibiting inflammation, and maintaining self-tolerance. In a variety of malignancies within the TME, Treg cells demonstrate notable flexibility and functional diversity. Highly plastic Treg cells can change into Th-like Treg cells in specific circumstances, which allow them to secrete particular pro-inflammatory cytokines. Interleukin 35 (IL-35) is a part of the immunosuppressive cytokines that belong to the IL-12 family. Treg cells release IL-35, which was elevated in the peripheral blood and TME of numerous cancer patients, implying that IL-35 in the TME may be an intriguing target for cancer therapy. In cancer, IL-35 is a two-edged sword; it promotes tumorigenicity in cancer cells while shielding them from apoptosis. Nonetheless, other investigations have mentioned its conflicting effects on cancer prevention. Herein, we provide an updated understanding of the critical mechanisms behind the anticancer immunity mediated by Treg cells plasticity, the role of IL-35, and tactics to strengthen the immune response against malignancies, outlining major clinical trials that used Treg cells/IL-35 therapies in the three main cancer types (lung, breast, and colorectal cancers).
T淋巴细胞是构成肿瘤微环境（TME）的免疫细胞之一，在肿瘤生长和抗肿瘤反应中起着至关重要的作用。调节性T细胞（Treg细胞）是免疫系统中CD4+T细胞的一个亚群，具有抑制免疫系统的作用。它们通过主转录因子叉头框蛋白P3（FOXP3）的表达而得以区分。此外，Treg细胞对于维持免疫稳态、抑制炎症以及维持自身耐受性至关重要。在TME中的多种恶性肿瘤中，Treg细胞表现出显著的可塑性和功能多样性。高度可塑性的Treg细胞在特定情况下可转变为Th样Treg细胞，使其能够分泌特定的促炎细胞因子。白细胞介素35（IL-35）是属于IL-12家族的免疫抑制细胞因子的一部分。Treg细胞释放IL-35，在众多癌症患者的外周血和TME中其水平升高，这意味着TME中的IL-35可能是癌症治疗中一个引人关注的靶点。在癌症中，IL-35是一把双刃剑；它在促进癌细胞致瘤性的同时，又能保护它们免于凋亡。尽管如此，其他研究也提到了它在癌症预防方面的矛盾作用。在此，我们对Treg细胞可塑性介导的抗癌免疫背后的关键机制、IL-35的作用以及增强针对恶性肿瘤免疫反应的策略提供了最新的认识，并概述了在三种主要癌症类型（肺癌、乳腺癌和结直肠癌）中使用Treg细胞/IL-35疗法的主要临床试验。
