Karan Dev
Department of Pathology, Medical College of Wisconsin, Milwaukee, WI, United States.
Front Oncol. 2021 Oct 4;11:727583. doi: 10.3389/fonc.2021.727583. eCollection 2021.
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.
内质网（ER）应激是细胞在应对应激刺激时保护功能活动的一种过程。然而，持续的内质网应激过度活跃会影响肿瘤的生长和发展。肝细胞富含内质网，极易受到内质网紊乱和应激的影响，这会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衍生的趋化因子会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患者的不良生存相关，并且可能是肝肿瘤细胞用来逃避免疫系统的一种机制。本文描述了CCL23在减轻内质网应激方面的潜在作用及其对促进抗肿瘤免疫的HCC肿瘤微环境的影响。此外，重新激活CCL23并结合免疫检查点阻断或化疗药物的方法可能为靶向肝细胞癌提供新的机会。
