RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Exploiting innate immunity for cancer immunotherapy.
Exploiting innate immunity for cancer immunotherapy.
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免疫疗法已革新多种癌症的治疗模式。然而,多数免疫调节策略聚焦于利用适应性免疫,例如通过免疫检查点阻断抑制免疫抑制信号,或通过双特异性T细胞衔接器和嵌合抗原受体(CAR)T细胞增强免疫刺激信号。尽管这些药物已取得很大成功,真正从免疫疗法中获益的患者仍只占少数。事实上,免疫疗效还取决于适应性免疫以外的肿瘤微环境多个组成部分。巨噬细胞、树突状细胞、髓源性抑制细胞、中性粒细胞、NK 细胞和非传统T细胞等先天免疫系统细胞,也参与癌症免疫逃逸和免疫监视。鉴于先天免疫是抗肿瘤免疫应答的基石,利用先天免疫为控制癌症提供了潜在治疗选择。目前,利用先天免疫的策略——如干扰素基因刺激因子激动剂、CAR-巨噬细胞或CAR-NK细胞疗法、代谢调节剂和新型免疫检查点阻断——已在临床前和临床研究中显示强效抗肿瘤活性。本文总结先天免疫细胞在抗肿瘤免疫中的潜在作用最新进展,并讨论靶向先天免疫系统治疗策略的发展。
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.
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