Cancer Center, Shanxi Bethune Hospital, Shanxi Academy of Medical Science, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, 030032, People's Republic of China.
Department of Breast Surgery, College of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, 310000, People's Republic of China.
Mol Cancer. 2023 Nov 27;22(1):187. doi: 10.1186/s12943-023-01885-w.
Immunotherapies have revolutionized the treatment paradigms of various types of cancers. However, most of these immunomodulatory strategies focus on harnessing adaptive immunity, mainly by inhibiting immunosuppressive signaling with immune checkpoint blockade, or enhancing immunostimulatory signaling with bispecific T cell engager and chimeric antigen receptor (CAR)-T cell. Although these agents have already achieved great success, only a tiny percentage of patients could benefit from immunotherapies. Actually, immunotherapy efficacy is determined by multiple components in the tumor microenvironment beyond adaptive immunity. Cells from the innate arm of the immune system, such as macrophages, dendritic cells, myeloid-derived suppressor cells, neutrophils, natural killer cells, and unconventional T cells, also participate in cancer immune evasion and surveillance. Considering that the innate arm is the cornerstone of the antitumor immune response, utilizing innate immunity provides potential therapeutic options for cancer control. Up to now, strategies exploiting innate immunity, such as agonists of stimulator of interferon genes, CAR-macrophage or -natural killer cell therapies, metabolic regulators, and novel immune checkpoint blockade, have exhibited potent antitumor activities in preclinical and clinical studies. Here, we summarize the latest insights into the potential roles of innate cells in antitumor immunity and discuss the advances in innate arm-targeted therapeutic strategies.
免疫疗法已经彻底改变了各种类型癌症的治疗模式。然而,这些免疫调节策略大多数都集中在利用适应性免疫上,主要通过免疫检查点阻断来抑制免疫抑制信号,或者通过双特异性 T 细胞衔接子和嵌合抗原受体 (CAR)-T 细胞来增强免疫刺激信号。尽管这些药物已经取得了巨大的成功,但只有一小部分患者能从免疫疗法中受益。实际上,免疫疗法的疗效取决于肿瘤微环境中除适应性免疫以外的多个组成部分。先天免疫系统的细胞,如巨噬细胞、树突状细胞、髓系来源的抑制细胞、中性粒细胞、自然杀伤细胞和非常规 T 细胞,也参与了癌症的免疫逃避和监视。鉴于先天免疫系统是抗肿瘤免疫反应的基石,利用先天免疫为癌症控制提供了潜在的治疗选择。到目前为止,利用先天免疫的策略,如干扰素基因刺激剂激动剂、CAR-巨噬细胞或 -自然杀伤细胞疗法、代谢调节剂和新型免疫检查点阻断,在临床前和临床研究中都显示出了强大的抗肿瘤活性。在这里,我们总结了先天细胞在抗肿瘤免疫中潜在作用的最新见解,并讨论了针对先天免疫系统的治疗策略的进展。
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