CCL23 in Balancing the Act of Endoplasmic Reticulum Stress and Antitumor Immunity in Hepatocellular Carcinoma.

CCL23 in Balancing the Act of Endoplasmic Reticulum Stress and Antitumor Immunity in Hepatocellular Carcinoma.
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DOI:
10.3389/fonc.2021.727583
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发表时间:
2021
影响因子:
4.7
通讯作者:
Karan D
Karan D
中科院分区:
医学3区
文献类型:
--
作者:
Karan D

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内质网(ER)应激是细胞响应应激刺激以保护功能活动的过程。然而,持续过度活跃的内质网应激会影响肿瘤的生长和发展。肝细胞富含 ER,并且极易受到 ER 扰动和应激的影响,从而导致免疫抑制以及侵袭性和耐药性肝细胞癌 (HCC) 的发展。内质网应激诱导的炎症和肿瘤来源的趋化因子影响肿瘤部位的免疫细胞组成。因此,肝肿瘤中 CCL23 趋化因子的减少与 HCC 患者的生存率较差有关,并且可能是肝肿瘤细胞用来逃避免疫系统的机制。本文描述了 CCL23 在缓解 ER 应激方面的前瞻性作用及其在促进抗肿瘤免疫方面对 HCC 肿瘤微环境的影响。此外,重新激活 CCL23 与免疫检查点阻断或化疗药物相结合的方法可能为靶向肝细胞癌提供新的机会。
Endoplasmic reticulum (ER) stress is a cellular process in response to stress stimuli in protecting functional activities. However, sustained hyperactive ER stress influences tumor growth and development. Hepatocytes are enriched with ER and highly susceptible to ER perturbations and stress, which contribute to immunosuppression and the development of aggressive and drug-resistant hepatocellular carcinoma (HCC). ER stress-induced inflammation and tumor-derived chemokines influence the immune cell composition at the tumor site. Consequently, a decrease in the CCL23 chemokine in hepatic tumors is associated with poor survival of HCC patients and could be a mechanism hepatic tumor cells use to evade the immune system. This article describes the prospective role of CCL23 in alleviating ER stress and its impact on the HCC tumor microenvironment in promoting antitumor immunity. Moreover, approaches to reactivate CCL23 combined with immune checkpoint blockade or chemotherapy drugs may provide novel opportunities to target hepatocellular carcinoma.
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