Local TLR4 stimulation augments in situ vaccination induced via local radiation and anti-CTLA-4 checkpoint blockade through induction of CD8 T-cell independent Th1 polarization.

We report the potential for MPL to augment the ISV effect of combination RT+C4 through FcγR, macrophage, and TBET⁺CD4⁺ Th1 cell dependent mechanisms. To our knowledge, this is the first report describing generation of a CD8⁺ T cell-independent, Th1 polarized, systemic antitumor immune response with subsequent generation of immunologic memory. These findings support the potential for vaccine adjuvants to enhance the efficacy of in situ tumor vaccine approaches.