The ability to mount an effective anti-tumor immune response requires coordinate control of CD4 T cell and CD8 T cell function by antigen presenting cells (APCs). Unfortunately, tumors create an immunosuppressive microenvironment that helps protect tumor cells from immune recognition. In many cases this defect can be traced back to a failure of APCs (most importantly dendritic cells (DCs)) to recognize, process, and present tumor antigens to T cells. In this review, we will summarize work addressing the role of different DC subsets in anti-tumor immunity and the various mechanisms used by tumor cells to suppress the ability of APCs to stimulate potent anti-tumor T cell responses.

March

The expression and turnover of Ag-specific peptide-MHC class II (pMHC-II) on the surface of dendritic cells (DCs) is essential for their ability to efficiently activate CD4 T cells. Ubiquitination of pMHC-II by the E3 ubiquitin ligase March-I regulates surface expression and survival of pMHC-II in DCs. We now show that despite their high levels of surface pMHC-II, MHC class II (MHC-II) ubiquitination-deficient mouse DCs are functionally defective; they are poor stimulators of naive CD4 T cells and secrete IL-12 in response to LPS stimulation poorly. MHC-II ubiquitination-mutant DC defects are cell intrinsic, and single-cell RNA sequencing demonstrates that these DCs have an altered gene expression signature as compared with wild-type DCs. Curiously, these functional and gene transcription defects are reversed by activating the DCs with LPS. These results show that dysregulation of MHC-II turnover suppresses DC development and function.