Immunotherapy with natural conventional type-1 dendritic cells excels at immune memory induction to eradicate cancer relapse

The potential of dendritic cell (DC) vaccination against cancer is not fully achieved. While next generation vaccines using adoptive transfer of natural DCs are explored, little is known about the precise nature of the anti-cancer immune response triggered by different natural DC subsets and their relevance in preventing postsurgical tumor recurrence. Here, we used mouse splenic conventional DC1s (cDC1s) or cDC2s pulsed with tumor cell lysates to generate DC vaccines. cDC1-based vaccination induced a stronger effector and memory CD4+ and CD8+ anti-tumor T cell response, leading to a better control of tumors treated either therapeutically or prophylactically. Using an experimental model of tumor relapse, we showed that adjuvant or neoadjuvant cDC1 vaccination improved anti-tumor immune memory, particularly by increasing the infiltrates of CD4+ tissue resident memory T cells. This translated into complete prevention of tumor relapses. Our findings suggest that cDC1-based vaccination excels at immune memory induction and prevention of cancer recurrence. Gene expression profile at single cell level of tumor infiltrating lymphocytes (TILs, including CD4+ and CD8+ T cells) from MC38 colorectal carcinoma cell line injected intradermally in C57BL/6 mice at day 5 of growth. CD4+ and CD8+ T cells from 4 groups: 1) primary tumors; 2) tumor rechallenge 30d after primary tumor resection; 3) tumor rechallenge 30d after primary tumor resection: neoadjuvant treatment of primary tumors with cDC1-based anti-cancer vaccination; 4) tumor rechallenge 30d after primary tumor resection: neoadjuvant treatment of primary tumors with anti-PD1. Two biological replicates (each a pool of 3 mice) for each experimental condition are analyzed. Multiplexing was done using CMO tags.