细胞毒性T细胞
溶瘤腺病毒
免疫疗法
肿瘤浸润淋巴细胞
生物
病毒
免疫检查点
T细胞
黑色素瘤
癌症免疫疗法
医学
癌症
抗原
病毒学
作者
Ibrahim Ragab Eissa,Nobuaki Mukoyama,Mohamed Abdelmoneim,Yoshinori Naoe,Shigeru Matsumura,Itzel Bustos-Villalobos,Toru Ichinose,Noriyuki Miyajima,Daishi Morimoto,Maki Tanaka,Yasushi Fujimoto,Michihiko Sone,Yasuhiro Kodera,Hideki Kasuya
摘要
Oncolytic viruses (OVs) remodel the tumor microenvironment by switching a cold tumor into a hot tumor with high CD8+ T-cell infiltration. CD8+ T-cell activity plays an essential role in the antitumor efficacy of OVs. However, the activity of T cells is impaired by the programmed cell death protein-1/programmed cell death-ligand 1 (PD-1/PD-L1) interaction. To date, it remains unclear why OVs alone have a significant antitumor activity even when PD-L1 expression persists on tumor or immune cells. In this study, we found that canerpaturev (C-REV) treatment significantly suppressed tumor growth, even though it induced a significant increase in PD-L1 expression in tumors in vivo as well as persistence of high PD-L1 expression on antigen-presenting cells (macrophage and dendritic cells [DCs]). Surprisingly, we observed that C-REV treatment increased the abundance of activated CD8+ PD-1- tumor-infiltrating lymphocytes (TILs) in the tumor on both the injected and contralateral sides, although infiltration of CD8+ PD-1high TILs into the tumor was observed in the control group. Moreover, the difference in PD-1 expression was observed only in tumors after treatment with C-REV, whereas most CD8+ T cells in the spleen, tumor-draining lymph nodes and blood were PD-1-negative, and this did not change after C-REV treatment. In addition, changes in expression of T-cell immunoglobulin and mucin-domain containing-3 and T-cell immune-receptor with Ig and ITIM domains were not observed on CD8+ TILs after C-REV treatment. Taken together, our findings may reveal mechanisms that allow OVs to trigger an antitumor immune response, irrespective of a PD-L1-enriched tumor microenvironment, by recruitment of CD8+ PD-1- TILs.
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