Dysregulation of Antigen Presenting Cell Function in Cancer

Division Of Basic Sciences - Nci

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Abstract

Antigen presenting cells (APC) function is suppressed in tumor bearing mice, with tumor infiltrating dendritic cells (DCs) displaying low levels of MHC-II and costimulatory signals that promote T cell tolerance to tumor antigens. Outside of the tumor, lymph node DCs are able to process and cross-present tumor antigens to tumor-specific CD8 T cells, however these DCs are unable to process and generate the MHC-II-peptide complexes required for CD4 T cell activation. We are currently characterizing the functional status of lymph node DC subsets in tumor-bearing mice and performing single cell RNA Sequence analysis to examine the gene expression profile of all DC subsets in tumor-draining and non-draining lymph nodes. We have found that tumor-draining lymph node DCs have diminished expression of MHC-class II (but not MHC class I) proteins and have reduced capacity for antigen capture, processing, and presentation. By analyzing gene expression in these cells we are identifying molecular pathways that are deficient in these cells. Our ultimate goal is to "correct" these APC defects (by generating genetically-altered DCs) that will allow efficient CD4 T cell priming and anti-tumor CD8 T cell responses.