Type I IFN Activating Type I Dendritic Cells for Antitumor Immunity

Abstract Immune checkpoint inhibitors are successful immunotherapy modalities that enhance CD8+ T-cell responses. Although T cells are initially primed in draining lymph nodes, the mechanisms that underlie their reactivation inside the tumor microenvironment are less clear. Recent studies have found that not only is the cross-priming of conventional type 1 dendritic cells (cDC1) required to initiate CD8+ T-cell responses during tumor progression, but it also plays a central role in immunotherapy-mediated reactivation of tumor-specific CD8+ T cells for tumor regression. Moreover, many cancer treatment modalities trigger type I IFN responses, which play critical roles in boosting cDC1 cross-priming and CD8+ T-cell reactivation. Inducing type I IFNs within tumors can overcome innate immune resistance and activate antitumor adaptive immunity. Here, we review recent studies on how type I IFN-cDC1 cross-priming reactivates CD8+ T cells and contributes to tumor control by cancer immunotherapy.