Identification of the Immediate Precursors of Tumor Dendritic Cells

The ontogeny of dendritic cells (DC) in tumors remains unclear. Our previous studies have shown that conventional DC (cDC) in murine lymphoid tissue and bone marrow arise from a distinct population of CD11c(+) MHC class II(−)lineage(−) immediate precursors, which are now known as pre‐cDC. In this study, we show that pre‐cDC are a key source of DC in experimental murine tumors. Pre‐cDC from tumors are replication‐competent and generate homogeneous cDC that continue to divide for several generations when co‐cultured on a supportive stromal monolayer. Adoptively transferred pre‐cDC, but not monocytes, generate DC in tumors. In vivo bromodeoxyuridine incorporation studies reveal that endogenous pre‐cDC and cDC are actively replicating in tumors. The chemokine, CCL3, was found to play a critical role in promoting pre‐cDC migration into tumors from the circulation. Collectively, our findings provide evidence of a distinct development pathway for cDC in tumors and highlight the importance of in situ replication of pre‐cDC and cDC in their expansion. The identification of this pathway is an important step in addressing how tumor microenvironments influence the developmental fate and function of DC.