Department of Pathology, Dalhousie University, Halifax, NS B3H 4R2, Canada.
Department of Microbiology and Immunology, Dalhousie University, Halifax, NS B3H 4R2, Canada.
Viruses. 2021 Apr 10;13(4):654. doi: 10.3390/v13040654.
Oncolytic reovirus preferentially targets and kills cancer cells via the process of oncolysis, and additionally drives clinically favorable antitumor T cell responses that form protective immunological memory against cancer relapse. This two-prong attack by reovirus on cancers constitutes the foundation of its use as an anticancer oncolytic agent. Unfortunately, the efficacy of these reovirus-driven antitumor effects is influenced by the highly suppressive tumor microenvironment (TME). In particular, the myeloid cell populations (e.g., myeloid-derived suppressive cells and tumor-associated macrophages) of highly immunosuppressive capacities within the TME not only affect oncolysis but also actively impair the functioning of reovirus-driven antitumor T cell immunity. Thus, myeloid cells within the TME play a critical role during the virotherapy, which, if properly understood, can identify novel therapeutic combination strategies potentiating the therapeutic efficacy of reovirus-based cancer therapy.
溶瘤病毒通过溶瘤作用优先靶向和杀伤癌细胞,此外还能诱导临床上有利的抗肿瘤 T 细胞反应,形成对癌症复发的保护性免疫记忆。这种溶瘤病毒对癌症的双重攻击构成了其作为抗肿瘤溶瘤剂的基础。不幸的是,这些由溶瘤病毒驱动的抗肿瘤作用的疗效受到高度抑制性肿瘤微环境 (TME) 的影响。特别是 TME 中具有高度免疫抑制能力的髓样细胞群体(例如,髓源性抑制细胞和肿瘤相关巨噬细胞)不仅影响溶瘤作用,而且还积极损害溶瘤病毒驱动的抗肿瘤 T 细胞免疫的功能。因此,TME 中的髓样细胞在病毒治疗中起着关键作用,如果能够正确理解,就可以确定增强基于溶瘤病毒的癌症治疗疗效的新的治疗联合策略。