CD5 expression by dendritic cells directs T cell immunity and sustains immunotherapy responses
Mingyu He, Kate Roussak, Feiyang Ma, Nicholas Borcherding, Vince Garin, J. Michael White, Charles R. Schutt, Trine I. Jensen, Yun Zhao, Courtney A. Iberg, Kairav Shah, Himanshi Bhatia, Daniel Korenfeld, Sabrina Dinkel, Judah Gray, Alina Ulezko Antonova, Stephen T. Ferris, David L. Donermeyer, Cecilia S. Lindestam Arlehamn, Matthew M. Gubin, Jingqin Luo, Laurent Gorvel, Matteo Pellegrini, Alessandro Sette, Thomas Tung, Rasmus O. Bak, Robert L. Modlin, Ryan C. Fields, Robert D. Schreiber, Paul M. Allen, Eynav Klechevsky
Abstract
The induction of proinflammatory T cells by dendritic cell (DC) subtypes is critical for antitumor responses and effective immune checkpoint blockade (ICB) therapy. Here, we show that human CD1c + CD5 + DCs are reduced in melanoma-affected lymph nodes, with CD5 expression on DCs correlating with patient survival. Activating CD5 on DCs enhanced T cell priming and improved survival after ICB therapy. CD5 + DC numbers increased during ICB therapy, and low interleukin-6 (IL-6) concentrations promoted their de novo differentiation. Mechanistically, CD5 expression by DCs was required to generate optimally protective CD5 hi T helper and CD8 + T cells; further, deletion of CD5 from T cells dampened tumor elimination in response to ICB therapy in vivo. Thus, CD5 + DCs are an essential component of optimal ICB therapy.