Mast cells infiltrate prostate tumors, suppress antigen specific T cells and promote the development of tolerogenic tumor associated dendritic cells

Wednesday, October 26, 2011 — Poster Session IV
2:00 p.m. – 4:00 p.m.	Natcher Conference Center	NCI	IMMUNO/INFLAM-31

* FARE Award Winner

Authors

• S Watkins
• A Hurwitz

Abstract

Immunotherapy is an attractive strategy for treating cancer. However, attempts to utilize this therapy have fallen short due to the loss of T cell function in tumors. To study the complex tumor microenvironment and suppression of immune cells we utilize the TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model. We have recently demonstrated a novel mechanism that tumor-associated DCs (TADC), but not wild-type prostate DCs, induce tolerance and suppressive activity in infiltrating T cells. This induction of tolerance is regulated by DC expression of FOXO3, a protein previously identified to be important for cell-cycle regulation. We have now identified a mechanism that promotes FOXO3 expression and tolerogenic functions in DC in that tumor-infiltrating mast cells produce increased levels of the cytokine IL-13. MC compose approximately 25% of the infiltrating CD45+ cells in advanced prostate tumors. Upon cross-linking the FcER, purified MC de-granulated and secreted increased levels of IL-13. Further, MC from tumors but not MC isolated from the peritoneum supported the differentiation of FOXO3+ tolerogenic DC via an IL-13 dependent mechanism. Our findings reveal novel mechanisms that promote immune tolerance in favor of anti-tumor immunity and provide promising targets for the enhancement of cancer immunotherapy.

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