Ishibashi Airi, Li Yue, Hisatomi Yuuta, Ohta Noriko, Uegaki Yuko, Tanemura Atsushi, Ohashi Riuko, Kitamura Koji, Saga Kotaro, Yoshimura Yasuhide, Inubushi Satoko, Ishida Kyoso, Iwabuchi Sadahiro, Hashimoto Shinichi, Kiyohara Eiji, Yagita Hideo, Kaneda Yasufumi, Nimura Keisuke
Division of Gene Therapy Science, Department of Genome Biology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
Division of Gene Therapy Science, Gunma University Initiative for Advanced Research, Gunma University, Maebashi, Gunma 371-8511, Japan.
Mol Ther Oncol. 2024 Oct 10;32(4):200893. doi: 10.1016/j.omton.2024.200893. eCollection 2024 Dec 19.
The tumor-infiltrating lymphocyte (TIL) is a crucial factor in controlling tumor growth. A therapeutic method activating TIL is desired for treating patients with metastatic tumors. Here, we show that treating a local tumor with a combination therapy of UV-irradiated hemagglutinating virus of Japan envelope (HVJ-E) plus agonist antibodies, including OX40, against T cell costimulatory molecules induces systemic anti-tumor effects in a T cell-dependent manner in multiple cancer cell lines. Transcriptome and T cell receptor repertoire analyses revealed that HVJ-E + anti-OX40 antibody treatment activates CD4 and CD8 T cells and promotes T cell trafficking between tumors. These systemic anti-tumor effects required an association between Nkg2d and Nkg2d ligands. Our findings provide insights into how systemic anti-tumor effects are induced and may help the development of therapeutic strategies for eliciting such effects.
肿瘤浸润淋巴细胞（TIL）是控制肿瘤生长的关键因素。对于治疗转移性肿瘤患者而言，需要一种激活TIL的治疗方法。在此，我们表明，用紫外线照射的日本血凝病毒包膜（HVJ-E）与包括OX40在内的针对T细胞共刺激分子的激动剂抗体联合治疗局部肿瘤，可在多种癌细胞系中以T细胞依赖性方式诱导全身抗肿瘤效应。转录组和T细胞受体库分析表明，HVJ-E +抗OX40抗体治疗可激活CD4和CD8 T细胞，并促进肿瘤之间的T细胞迁移。这些全身抗肿瘤效应需要Nkg2d与Nkg2d配体之间的关联。我们的研究结果为全身抗肿瘤效应的诱导方式提供了见解，并可能有助于开发引发此类效应的治疗策略。
