Dendritic cell redundancy enables priming of anti-tumor CD4 T cells in pancreatic cancer

Here, we combine an innate immune adjuvant with anti-CTLA-4 and anti-PD-1 to achieve durable remissions and immunologic memory in multiple mouse models of poorly immunogenic PDAC. Tumor regression does not depend on CD8 T cells or tumor cell MHC class I expression but instead requires IFNγ-producing CD4 T cells (Th1s) that were primed by dendritic cells in lymph nodes.

Combination immunotherapy induces an influx of activated cDC2s carrying tumor antigen into tumor-draining lymph nodes; cDC2s are required for orthotopic tumor clearance. Intratumoral CD4 T cells and cDC2s remain present in treatment-naïve and chemotherapy-exposed human PDAC. Even in chemotherapy-exposed patients’ blood, cDC2s outnumber cDC1s by ten-fold.