Mardi Amirhossein, Shirokova Anastasia V, Mohammed Rebar N, Keshavarz Ali, Zekiy Angelina O, Thangavelu Lakshmi, Mohamad Talar Ahmad Merza, Marofi Faroogh, Shomali Navid, Zamani Amir, Akbari Morteza
Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Prosthetic Dentistry, I. M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia.
Cancer Cell Int. 2022 Apr 29;22(1):168. doi: 10.1186/s12935-022-02585-z.
Chimeric antigen receptor (CAR) T-cell therapy is a promising and rapidly expanding therapeutic option for a wide range of human malignancies. Despite the ongoing progress of CAR T-cell therapy in hematologic malignancies, the application of this therapeutic strategy in solid tumors has encountered several challenges due to antigen heterogeneity, suboptimal CAR T-cell trafficking, and the immunosuppressive features of the tumor microenvironment (TME). Oncolytic virotherapy is a novel cancer therapy that employs competent or genetically modified oncolytic viruses (OVs) to preferentially proliferate in tumor cells. OVs in combination with CAR T-cells are promising candidates for overcoming the current drawbacks of CAR T-cell application in tumors through triggering immunogenic cell death (ICD) in cancer cells. ICD is a type of cellular death in which danger-associated molecular patterns (DAMPs) and tumor-specific antigens are released, leading to the stimulation of potent anti-cancer immunity. In the present review, we discuss the biological causes of ICD, different types of ICD, and the synergistic combination of OVs and CAR T-cells to reach potent tumor-specific immunity.
嵌合抗原受体（CAR）T细胞疗法是一种前景广阔且迅速发展的治疗选择，适用于多种人类恶性肿瘤。尽管CAR T细胞疗法在血液系统恶性肿瘤方面不断取得进展，但由于抗原异质性、CAR T细胞归巢欠佳以及肿瘤微环境（TME）的免疫抑制特性，这种治疗策略在实体瘤中的应用面临诸多挑战。溶瘤病毒疗法是一种新型癌症治疗方法，它利用有活性的或经过基因改造的溶瘤病毒（OVs）在肿瘤细胞中优先增殖。OVs与CAR T细胞联合使用有望克服当前CAR T细胞在肿瘤应用中的缺点，通过触发癌细胞中的免疫原性细胞死亡（ICD）来实现。ICD是一种细胞死亡类型，其中会释放危险相关分子模式（DAMPs）和肿瘤特异性抗原，从而刺激强大的抗癌免疫反应。在本综述中，我们讨论了ICD的生物学原因、不同类型的ICD以及OVs与CAR T细胞的协同组合，以实现强大的肿瘤特异性免疫。
