OX40+ plasmacytoid dendritic cells in the tumor microenvironment promote antitumor immunity.

Plasmacytoid dendritic cells (pDC), the major producers of Type I interferon, are principally recognized as key mediators of antiviral immunity. However, their role in tumor immunity is less clear. Depending on the context, pDC can both promote or suppress antitumor immune responses. In this study, we identified a naturally occurring pDC subset expressing high levels of OX40 (OX40+ pDC) enriched in the tumor microenvironment (TME) of head and neck squamous cell carcinoma. OX40+ pDC were distinguished by a distinct immunostimulatory phenotype, cytolytic function and ability to synergize with conventional dendritic cells (cDC) in generating potent tumor antigen-specific CD8+ T cell responses. Transcriptomically, we found they selectively utilized EIF2 signaling and oxidative phosphorylation pathways. Moreover, depletion of pDC in the murine OX40+ pDC-rich tumor model accelerated tumor growth. Collectively, we present evidence of a pDC subset in the TME that favors antitumor immunity.