12:00pm - 1:00pm|
Department of Microbiology & Immunology Seminar Series
Jose R Conejo-Garcia, MD, PhD
Professor and Program Leader, Tumor Microenvironment and Metastasis Program, The Wistar Institute
" Microbial driven TLR5-dependent signaling governs distal malignant progression through systemic tumor-promoting inflammation "
Host: Edith Lord
Seminar Abstract: The dominant R392X TLR5 polymorphism abrogates flagellin responses in >7% of humans. We report that TLR5-dependent commensal bacteria drive malignant progression at (distal) extra-mucosal locations by promoting systemic IL-6 up-regulation, which drives MDSC mobilization. Mechanistically, expanded granulocytic MDSCs cause γδ lymphocytes in TLR5+/+ tumors to secrete galectin-1, dampening anti-tumor immunity and accelerating malignant progression. In contrast, IL-17 is consistently up-regulated in TLR5-unresponsive tumor-bearing individuals, but only accelerates malignant progression in IL-6-unresponsive tumors. Importantly, depletion of commensal bacteria abrogates any TLR5-dependent differences in tumor growth. Contrasting differences in inflammatory cytokines and malignant evolution are recapitulated in TLR5-responsive/unresponsive ovarian and breast cancer patients. Therefore, inflammation, anti-tumor immunity and the clinical outcome of cancer patients are influenced by a common TLR5 polymorphism.
|Location: ||Upper Auditorium, Rm 3-7619|
Posted by: Nicole Beaumont, Micro & Immunolgy, 2-Mar-15 10:53am ET