CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Local treatment of HVJ-E with T cell costimulatory molecule stimulation elicits systemic anti-tumor effects.
Local treatment of HVJ-E with T cell costimulatory molecule stimulation elicits systemic anti-tumor effects.
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TIL(肿瘤浸润淋巴细胞)是控制肿瘤生长的关键因素。人们需要能够活化TIL的治疗方法,以治疗转移性肿瘤患者。本研究显示,在多种癌细胞系中,局部肿瘤接受经紫外线照射的血凝性日本脑炎病毒包膜(HVJ-E)与激动性抗体(包括针对T细胞共刺激分子OX40的抗体)联合治疗,可通过依赖T细胞的方式诱导全身性抗肿瘤效应。转录组和T细胞受体库分析显示,HVJ-E联合抗OX40抗体可活化CD4和CD8 T细胞,并促进T细胞在不同肿瘤间迁移。这些全身性抗肿瘤效应依赖NKG2D与其配体之间的结合。我们的发现揭示了诱导全身性抗肿瘤效应的机制,可为开发诱发此类效应的治疗策略提供帮助。
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.
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