Intratumoral NKT cell accumulation promotes antitumor immunity in pancreatic cancer

Here, using the mouse KRT19-deficient (sgKRT19-edited) PDA model, we find that intratumoral accumulation of natural killer T (NKT) cells are required to establish an immunologically active TME. Mechanistically, intratumoral NKT cells facilitate type I interferon (IFN) production to initiate an anti-tumor adaptive immune response, and orchestrate the intratumoral infiltration of T cells, dendritic cells, natural killer cells and myeloid-derived suppressor cells. At the molecular level, NKT cells promote the production of type I IFN through the interaction of their CD40L with CD40 on myeloid cells. To evaluate the theraputical potential of these observations, we find that administration of folinic acid to mice bearing PDA increases NKT cells in the TME and improves their response to anti-PD-1 antibody treatment. In conclusion, NKT cells have an essential role in the immune response to mouse PDA and are potential targets for immunotherapy. To investigate the impact of folinic acid (FA) treatment on tumor microenvironment, we performed gene expression profiling analysis by using bulk-RNAseq data of s.c. PDA tumors islodated from FA- and PBS-treated mice.