Dissecting the Tumor Myeloid Compartment Reveals Rare Activating Antigen-Presenting Cells Critical for T Cell Immunity

• Mouse and human tumors contain rare DCs that are stimulatory for T cells
• Stimulatory DCs are programmed through unique cytokines and transcription factors
• CD103+ DCs are sparse proximal to tumor margins but plentiful in distal regions
• Tumoral DCs are necessary for T-cell-mediated tumor rejection and predict survival

SummaryIt is well understood that antigen-presenting cells (APCs) within tumors typically do not maintain cytotoxic T cell (CTL) function, despite engaging them. Across multiple mouse tumor models and human tumor biopsies, we have delineated the intratumoral dendritic cell (DC) populations as distinct from macrophage populations. Within these, CD103+ DCs are extremely sparse and yet remarkably capable CTL stimulators. These are uniquely dependent on IRF8, Zbtb46, and Batf3 transcription factors and are generated by GM-CSF and FLT3L cytokines. Regressing tumors have higher proportions of these cells, T-cell-dependent immune clearance relies on them, and abundance of their transcripts in human tumors correlates with clinical outcome. This cell type presents opportunities for prognostic and therapeutic approaches across multiple cancer types.

Graphical AbstractFigure optionsDownload high-quality image (412 K)Download as PowerPoint slide