The site of tumor development determines immunogenicity via temporal mobilization of antigen-laden dendritic cells in draining lymph nodes

The elimination of solid tumors largely depends on effective T-cell priming by dendritic cells (DCs). For decades, studies focusing on antitumoral immune responses have been performed with tumors transplanted subcutaneously (s.c.). These studies however do not take into account the heterogeneous tissue distribution and functionality of the different DC subsets. Given the crucial role of DCs in inducing protective immune response, we postulated that the anatomic location of tumor development may greatly impact tumor immunogenicity. We therefore implanted tumor cells either in the DC-rich dermis environment or in the s.c. tissue that mainly contains macrophages and monocytes. We showed that intradermal (i.d.), but not s.c. tumors are rapidly rejected in a T-cell-dependent manner and induce protective T-cell responses. The rejection of i.d. tumors correlates with rapid recruitment of dermal DCs presenting the tumor antigen to both CD4 and CD8 T cells in the draining lymph nodes (dLNs). The same DC subsets were mobilized upon s.c. tumor transplantation but with delayed kinetics. Altogether, our results show that the anatomical site of tumor development influences tumor immunogenicity, notably by controlling the kinetics of DC mobilization in the draining LNs.