Overlapping and Distinct Mechanisms of Effective Neoantigen Cancer Vaccines and Immune Checkpoint Therapy.

Neoantigen vaccines utilize distinct cellular mechanisms from anti-CTLA-4 or anti-PD-1 immune checkpoint therapy.Neoantigen vaccines preferentially induce PD-1+ TCF1+ stem-like and proliferating neoantigen-specific CD8 T cellsAnti-PD-1 expands PD-1+ TCF-7-NeoAg-specific Teff/Tex, with combination anti-PD-1 + anti-CTLA-4 ICT inducing robust expansion of Bhlhe40hi PD-1+ TCF-7-NeoAg-specific Teff/Tex.Anti-CTLA-4 promotes Th1-like ICOS+ Bhlhe40+ CD4 T cells, while combination anti-CTLA-4 and anti-PD-1 ICT induces a small subset of Th2-like CD4 T cellsNeoantigen vaccines induce partially distinct intratumoral macrophage remodeling from immune checkpoint therapyNeoantigen vaccines in combination with anti-CTLA-4 or anti-PD-1 provides enhanced tumor protection equivalent to or even exceeding protection seen with combination anti-CTLA-4 and anti-PD-1.