ZIA BC 011687 (ZIA) | |||
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Title | Dysregulation of Antigen Presenting Cell Function in Cancer | ||
Institution | NCI, Bethesda, MD | ||
Principal Investigator | Roche, Paul | NCI Program Director | N/A |
Cancer Activity | N/A | Division | CCR |
Funded Amount | $248,758 | Project Dates | null - null |
Fiscal Year | 2018 | Project Type | Intramural |
Research Topics w/ Percent Relevance | Cancer Types w/ Percent Relevance | ||
Cancer (100.0%) |
Bladder (10.0%) Urinary System (10.0%) |
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Research Type | |||
Vaccines Localized Therapies - Discovery and Development |
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Abstract | |||
The inability of the host immune system to recognize and eliminate tumor cells is well known. While much of this defect is attributed to the relative paucity of tumor-specific T cells, many tumor cells create a locally immunosuppressive environment by reduced secretion of inflammatory cytokines, increased secretion of anti-inflammatory cytokines, and increased infiltration of regulatory T cells. APC function is also suppressed in tumor bearing mice, with tumor infiltrating DCs displaying low levels of MHC-II and costimulatory signals that promote T cell tolerance to tumor antigens. Outside of the tumor itself, it has been reported that 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. The inability of the DCs to prime and license CD4 T cells to provide CD8 T cell effector function is therefore thought to be a major roadblock in generating anti-tumor responses. Given our interest in the cell biology of MHC-II-restricted antigen processing and presentation, we are characterizing the functional status of lymph node DC subsets in tumor-bearing mice with a particular emphasis on identifying and ""correcting"" APC defects (by generating genetically-altered DCs) that will allow efficient CD4 T cell priming and anti-tumor CD8 T cell responses. We have published a literature review of studies examining antigen presentation defects in cancer and have unpublished findings revealing differences in gene expression in DC subsets from tumor draining lymph nodes as compared to normal DCs using FACS and RNA-Seq analysis. |