Jin Jin, Cheng Jiali, Huang Meijuan, Luo Hui, Zhou Jianfeng
Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan, Hubei, China.
Immunotherapy Research Center for Hematologic Diseases of Hubei Province Wuhan, Hubei, China.
Am J Cancer Res. 2020 Dec 1;10(12):4038-4055. eCollection 2020.
Chimeric antigen receptor (CAR)-T therapy started a new era of tumor treatment, especially for hematological malignancies. However, many challenges remain, including low-level proliferation and short-term persistence, insufficient CAR T-cell trafficking, suppressive tumor microenvironment (TME), frequent adverse events and the unaffordable manufacturing process. Cytokines are pleiotropic hormones involved in multiple processes of immunity, including activation, expansion, differentiation, and migration of immune cells. Both pre-clinical models and clinical trials showed that armoring CAR-T cells with cytokines strengthened the anti-tumor responses of CAR T cells. This review looked into the key role of cytokines as a promoter of anti-tumor activities of CAR-T cells and consequently a facilitator of clinical translation, mainly, from cytokines of the common γ-chains family, chemokines and chemokine receptors, immunosuppressive molecules and pro-inflammatory cytokines.
嵌合抗原受体(CAR)-T细胞疗法开启了肿瘤治疗的新时代,尤其是对于血液系统恶性肿瘤。然而,仍然存在许多挑战,包括低水平增殖和短期持久性、CAR T细胞归巢不足、抑制性肿瘤微环境(TME)、频繁的不良事件以及难以承受的生产过程。细胞因子是多效性激素,参与免疫的多个过程,包括免疫细胞的激活、扩增、分化和迁移。临床前模型和临床试验均表明,用细胞因子武装CAR-T细胞可增强CAR T细胞的抗肿瘤反应。本综述探讨了细胞因子作为CAR-T细胞抗肿瘤活性促进剂以及临床转化促进剂的关键作用,主要涉及常见γ链家族的细胞因子、趋化因子和趋化因子受体、免疫抑制分子和促炎细胞因子。
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