Immune check-point blockade (ICB) has revitalized cancer immunotherapy, showing unprecedented efficacy despite only a narrow number of indications and with limited long-term protection. Cancer vaccines are promising combination partners for ICB to widen the patient population profiting from these treatments. Therapeutic heterologous prime-boost vaccination with KISIMATMprotein vaccine and VSV-GP-TAg oncolytic virus was shown to inflame the tumor microenvironment, promoting significant infiltration of antigen-specific CD8 T cells resulting in robust antitumoral efficacy in mouse tumor models, and clinical trials are currently ongoing. Here, we report the impact of NKG2A blockade on antitumoral CD8 T cell immune response elicited by KISIMA—VSV-GP-TAg vaccination in tumor mouse models. Combination therapy significantly reduced the amount of vaccine-induced exhausted CD8 T cells infiltrating the tumor, resulting in short-term improved tumor growth control and prolonged mouse survival, while it also influenced the establishment of systemic effector memory CD8 T cell response. Taken together, these data show a compartment-dependent effect of NKG2A blockade on cancer vaccine-induced T cell immunity, increasing intratumoral T cell efficacy and attenuating the development of peripheral effector memory CD8 T cell response.
免疫检查点阻断疗法（ICB）已重振癌症免疫治疗领域，尽管其适应症范围有限且长期保护效果不足，但仍展现出前所未有的疗效。癌症疫苗作为ICB的联合治疗伙伴，有望扩大受益于此类治疗的患者群体。KISIMA™蛋白疫苗与VSV-GP-TAg溶瘤病毒构成的异源初免-加强治疗方案，在小鼠肿瘤模型中证实可激活肿瘤微环境，显著促进抗原特异性CD8 T细胞浸润，从而产生强大的抗肿瘤效应，相关临床试验目前正在进行中。本研究报道了NKG2A阻断对KISIMA-VSV-GP-TAg疫苗在荷瘤小鼠模型中诱导的抗肿瘤CD8 T细胞免疫应答的影响。联合治疗显著减少了疫苗诱导的耗竭性CD8 T细胞在肿瘤内的浸润，短期内改善了肿瘤生长控制并延长了小鼠生存期，同时影响了系统性效应记忆CD8 T细胞应答的建立。综上所述，这些数据表明NKG2A阻断对癌症疫苗诱导的T细胞免疫具有区室依赖性效应：既能增强肿瘤内T细胞效能，又会削弱外周效应记忆CD8 T细胞应答的发展。
肿瘤(癌症)患者之家