TLR5 mediated regulation of tumor growth in an inducible model of cancer (162.48)

• Published in: The Journal of immunology (1950) Vol. 188; no. 1_Supplement; pp. 162 - 162.48
• Main Authors: Rutkowski, Melanie, Escovar-Fadul, Ximena, Sarmin, Fahmida, Stephen, Tom, Allegrezza, Michael, Gil-Guerva, Oswaldo, Tesone, Amelia, Conejo-Garcia, Jose
• Format: Journal Article
• Language: English
• Published: 01.05.2012
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.188.Supp.162.48

Abstract It has been reported that up to 25% of the human population carries a dominant point mutation in TLR5 resulting in the loss of TLR5 signaling. TLR5 expression is paramount in modulating the balance of regulatory FoxP3+ and proinflamatory IL-17+ T cell lineages, two cellular subsets with potentially divergent roles in cancer. However, in the context of cancer, the significance of this mutation remains unknown. Sequencing of cDNA isolated from human ovarian tumor specimens revealed that 6% of tumor specimens harbor a functional mutation in TLR5, suggesting that a loss in TLR5 signaling results in “resistance” to cancer. To further investigate the role of TLR5 signaling in cancer progression, we utilized a novel p53 and KRas dependent model of inducible cancer. TLR5-/- mice had a remarkable delay in tumor onset and a dramatic reduction in tumor burden. Corresponding to the delayed tumor onset, we observed that T cells sorted from the tumor draining lymph nodes of TLR5-/- mice were able to vigorously recall against tumor antigens compared to a profound paralysis of effector function in T cells sorted from the draining lymph nodes of WT mice. These data indicate for the first time that pattern recognition receptors may influence the elimination and/or equilibrium phases of tumor progression at extraintestional locations, pinpointing potentially novel pathways to target for immunotherapy.