Despite the clinical success of immune checkpoint blockade, only a subset of people exhibits durable responses, suggesting that an alternative immunotherapeutic strategy is required. This paper reported a two-in-one cancer vaccine that targets programmed death ligand 1 (PDL1) that blocks the PD1/PDL1 pathway and also activates antitumor immune response. The PDL1- NitraTh vaccine, which consists of the extracellular domain of PDL1 and nitrated T cell epitope, effectively broke the immune tolerance of PDL1 and elicited PDL1-specific humoral and cellular immunity. The treatment of PDL1-NitraTh exhibited potent antitumor activity. Moreover, immunization of PDL1 vaccine increased the infiltration of tumor lymphocytes and decreased the proportion of Treg cells in tumor tissues, suggesting that the vaccine may remodel the tumor microenvironment. The upregulation of PDL1 in tumor tissues was induced by PDL1-NitraTh vaccine but not in spleen and lymphomas. This upregulation of PDL1 is beneficial to the antitumor activity of PDL1-specific humoral and cellular immunity induced by PDL1-NitraTh. In summary, PDL1-targeted vaccine exhibits potent antitumor activity and may provide an alternative immunotherapy strategy for patients who are not sensitive to PDL1 antibody drugs.

中文翻译：

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通过同时阻断PD1 / PDL1途径并激活PDL1特异性免疫反应，靶向PDL1的疫苗具有强大的抗肿瘤活性。

尽管免疫检查点封锁在临床上取得了成功，但只有一部分人表现出持久的反应，这表明需要一种替代的免疫治疗策略。本文报道了一种针对计划死亡配体1（PDL1）的二合一癌症疫苗，该疫苗可阻断PD1 / PDL1途径并激活抗肿瘤免疫反应。由PDL1的胞外域和硝化T细胞表位组成的PDL1- NitraTh疫苗有效地破坏了PDL1的免疫耐受性，并引发了PDL1特异性的体液和细胞免疫。PDL1-NitraTh的治疗表现出有效的抗肿瘤活性。此外，免疫PDL1疫苗可增加肿瘤淋巴细胞的浸润，并降低肿瘤组织中Treg细胞的比例，这表明该疫苗可能会重塑肿瘤微环境。PDL1-NitraTh疫苗诱导了肿瘤组织中PDL1的上调，但脾脏和淋巴瘤中却没有。PDL1的这种上调有利于PDL1-NitraTh诱导的PDL1特异性体液和细胞免疫的抗肿瘤活性。总之，针对PDL1的疫苗具有强大的抗肿瘤活性，并且可以为对PDL1抗体药物不敏感的患者提供替代的免疫治疗策略。