Abstract 3659: Mast cell interactions with T-regulatory cells determine the outcome of colon cancer

Abstract

Abstract Mast cells (MCs) are a bone marrow-derived, long-lived, heterogeneous cellular population that act both as positive and negative regulators of immune responses. They are arguably the biggest chemical factory in the body, and influence other cells through both soluble mediators and cell to cell interaction. MCs are commonly seen in various tumors and have been attributed alternatively with tumor rejection or promotion properties. Tumor infiltrating MCs are derived both from sentinel resident MC progenitors as well as from recruited progenitor cells (1). MC directly influence tumor cell proliferation and invasion (2, 3), but also help shape the tumor microenvironment (1) and modulate immune responses to tumors. Best known for orchestrating inflammation and angiogenesis, the role of MCs in modulating adaptive immune responses has only recently attracted attention. MCs are responsible for expansion of lymph nodes, and recruitment of dendritic cells. MC mediate immune suppression by Treg but can also reverse suppressive properties of Treg (4) or convert Treg into TH17 pro-inflammatory cells The central role of MC in the control of innate and adaptive immunity endows them with the ability to tune the nature of host responses to cancer and ultimately determine the outcome of disease and fate of the cancer patient (5) (6). 1. Maltby S, Khazaie K, McNagny KM. Mast cells in tumor growth: Angiogenesis, tissue remodelling and immune-modulation. Biochim Biophys Acta. 2009;1796(1):19-26. PMCID: 2731828. 2. Strouch MJ, Cheon EC, Salabat MR, Krantz SB, Gounaris E, Melstrom LG, et al. Crosstalk between mast cells and pancreatic cancer cells contributes to pancreatic tumor progression. Clin Cancer Res. 2010;16(8):2257-65. 3. Cheon EC, Khazaie K, Khan MW, Strouch MJ, Krantz SB, Phillips J, et al. Mast cell 5-Lipoxygenase activity promotes intestinal polyposis in APCΔ468 mice. Cancer Research. 2010;(in press). 4. Gounaris E, Blatner NR, Dennis K, Magnusson F, Gurish MF, Strom TB, et al. T-regulatory cells shift from a protective anti-inflammatory to a cancer-promoting proinflammatory phenotype in polyposis. Cancer Res. 2009;69(13):5490-7. 5. Blatner NR, Bonertz A, Beckhove P, Cheon EC, Krantz SB, Strouch M, et al. In colorectal cancer mast cells contribute to systemic regulatory T-cell dysfunction. Proc Natl Acad Sci U S A. 2010;107(14):6430-5. PMCID: 2851977. 6. Colombo MP, Piconese S. Polyps Wrap Mast Cells and Treg within Tumorigenic Tentacles. Cancer Res. 2009. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3659. doi:10.1158/1538-7445.AM2011-3659