Ayele Kalkidan, Wakimoto Hiroaki, Nauwynck Hans J, Kaufman Howard L, Rabkin Samuel D, Saha Dipongkor
Department of Pharmaceutical and Biomedical Sciences, California Northstate University College of Pharmacy, Elk Grove, CA 95757, USA.
Brain Tumor Research Center, Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Mol Ther. 2025 Apr 2;33(4):1327-1343. doi: 10.1016/j.ymthe.2024.12.054. Epub 2024 Dec 30.
Oncolytic herpes simplex viruses (oHSV) preferentially replicate in cancer cells while inducing antitumor immunity, and thus, they are often referred to as in situ cancer vaccines. OHSV infection of tumors elicits diverse host immune responses comprising both innate and adaptive components. Although the innate and adaptive immune responses primarily target the tumor, they also contribute to antiviral immunity, limiting viral replication/oncolysis. OHSV-encoded proteins use various mechanisms to evade host antiviral pathways and immune recognition, favoring oHSV replication, oncolysis, and spread. In general, oHSV infection and replication within tumors results in a series of sequential events, such as oncolysis and release of tumor and viral antigens, dendritic cell-mediated antigen presentation, T cell priming and activation, T cell trafficking and infiltration to tumors, and T cell recognition of cancer cells, leading to tumor (and viral) clearance. These sequential events align with all steps of the cancer-immunity cycle. However, a comprehensive understanding of the interplay between oHSV and host immune responses is crucial to optimize oHSV-induced antitumor immunity and efficacy. Therefore, this review aims to elucidate oHSV's communication with innate and adaptive immune systems and use such interactions to improve oHSV's potential as a potent immunovirotherapeutic agent against cancer.
溶瘤单纯疱疹病毒（oHSV）优先在癌细胞中复制，同时诱导抗肿瘤免疫，因此，它们常被称为原位癌疫苗。肿瘤的oHSV感染引发多种宿主免疫反应，包括先天免疫和适应性免疫成分。尽管先天免疫和适应性免疫反应主要针对肿瘤，但它们也有助于抗病毒免疫，限制病毒复制/溶瘤作用。oHSV编码的蛋白利用各种机制逃避宿主抗病毒途径和免疫识别，有利于oHSV的复制、溶瘤和传播。一般来说，oHSV在肿瘤内的感染和复制会导致一系列连续事件，如肿瘤和病毒抗原的溶瘤和释放、树突状细胞介导的抗原呈递、T细胞致敏和激活、T细胞向肿瘤的运输和浸润，以及T细胞对癌细胞的识别，从而导致肿瘤（和病毒）清除。这些连续事件与癌症免疫循环的所有步骤一致。然而，全面了解oHSV与宿主免疫反应之间的相互作用对于优化oHSV诱导的抗肿瘤免疫和疗效至关重要。因此，本综述旨在阐明oHSV与先天免疫系统和适应性免疫系统的相互作用，并利用这种相互作用提高oHSV作为一种有效的抗癌免疫病毒治疗剂的潜力。
