[HTML][HTML] OX40+ plasmacytoid dendritic cells in the tumor microenvironment promote antitumor immunity

K Poropatich, D Dominguez, WC Chan… - The Journal of …, 2020 - Am Soc Clin Investig
K Poropatich, D Dominguez, WC Chan, J Andrade, Y Zha, B Wray, J Miska, L Qin, L Cole…
The Journal of clinical investigation, 2020Am Soc Clin Investig
Plasmacytoid DCs (pDCs), 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, pDCs can 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+ pDCs were distinguished by a distinct …
Plasmacytoid DCs (pDCs), 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, pDCs can 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+ pDCs were distinguished by a distinct immunostimulatory phenotype, cytolytic function, and ability to synergize with conventional DCs (cDCs) in generating potent tumor antigen–specific CD8+ T cell responses. Transcriptomically, we found that they selectively utilized EIF2 signaling and oxidative phosphorylation pathways. Moreover, depletion of pDCs 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.
The Journal of Clinical Investigation