Anti-PD1 during T cell priming enhances long-term protection against metastatic tumors by epigenetically tuning T cell exhaustion

However, it remains unclear which T cell fate best supports long-term immunity following initial tumor clearance or surgical resection when antigen is largely absent. To determine which T cell fate provides durable protection following surgical tumor removal and metastatic rechallenge, we modulated T cell priming using anti-PD-1, IFN-b or agonistic anti-CD40 and assessed effects on CD8+ T cell differentiation and overall survival.

Strikingly, only treatment with anti-PD-1 but not IFN-b or anti-CD40 promoted improved long-term protection over surgical removal alone. Transcriptional and epigenetic profiling revealed that a circulatory, memory-like state sharing features of exhaustion characterizes the anti-tumor response during metastatic challenge in mice treated with anti-PD-1 and is associated with durable anti-tumor immunity.