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Sergei Grivennikov, Ph.D.Assistant Professor, Lewis Katz School of Medicine Temple Health, Fox Chase Cancer Center will present “Microbes and Cytokines Regulating Tumor Elicited Inflammation." Felix Yarovinsky will host.

Seminar Abstract: Tumor can induce recruitment of inflammatory cells as a part of so called “tumor-elicited inflammation” (TEI). Cytokines, produced by inflammatory cells and acting on cancer cells, provide a targetable link between inflammation and cancer. In colorectal cancer (CRC) we demonstrated that oncogenic events essential for tumor initiation inevitably lead to the local defects in epithelial barrier and commensal bacteria dependent production of pro-tumorigenic cytokine IL-17A, which regulates epithelial regeneration and tumorigenesis.  We found that IL-23 and IL-1 cytokine signaling represent a complimentary mechanism for IL-17A induction from multiple cell types and these mechanisms are very similar and conserved between the processes of epithelial injury and healing and intestinal tumor growth. Using genetic mouse models of CRC, we found distinct bacteria tightly adherent to cancerous tissue as well as distinct bacteria “pathways” associated with tumorigenesis.  These bacteria specifically adhere to tumor cells and can be recognized by specialized subsets of macrophages and monocytes to initiate secretion of cytokines. These cytokines, including some from IL-1 and IL-23 families drive several distinct pro-tumorigenic processes, including direct stimulation of epithelial cells and amplification of tumor-specific inflammation.  Distinct arms of IL-1 signaling help to keep detrimental microbiota in check, to prevent overt inflammation and accelerated tumor growth. Altogether, microbe driven tumor elicited inflammation is essential for tumor progression.

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