Sergei Grivennikov, PhD
Member & Assistant Professor
Office Phone: 215-214-3974
It has become recently clear that Inflammation plays important roles at different stages of tumor development, including initiation, promotion, malignant conversion, invasion, and metastasis. Immune cells that infiltrate tumors engage in an extensive and dynamic crosstalk with cancer cells and some of the molecular events that mediate this dialog have been revealed. Inflammatory microenvironment is an essential component of all tumors, including some in which a direct causal relationship with inflammation is not yet proven. Importantly, only a minority of all cancers are caused by germline mutations, whereas the vast majority (90%) are linked to somatic mutations or epigenetic changes and environmental factors, including preceding chronic inflammation. Recent studies provided further evidence about the connection between inflammation and cancer, as non-steroid anti-inflammatory drugs such as aspirin, significantly lower the risk of cancer death. Several types of tumor-associated inflammation have been outlined, which either pro- or anti-tumorigenic effect. Given the importance of the functional interaction between immune cells and cancer cells, the outstanding question is what mediates such a cross-talk?
Our research interests are to connect various immune signaling pathways with pathogenesis of inflammation-associated and sporadic cancers, including colon cancer.
Research in the lab utilizes various genetic animal models of immunodeficiency and cancer as well as human tissues and follows several major directions:
- Examine the role of various inflammatory cytokine pathways in tumor growth, invasion and metastasis
- Explore the mechanisms of how inflammatory response in the tumors is induced, including potential contribution of microbiota and endogenous factors produced by the host.
- How manipulations with the strength and specificity of the host inflammatory response may aid to the development of better preventive and therapeutic strategies.
Fox Chase Programs
- Posocco D, Dmitrieva O, Grivennikov SI. Microbiome Implications in Intestinal Tumorigenesis. Springer, volume "Intestinal Tumorigenesis". 2014. (In Press)
- Koltsova EK, Grivennikov SI. IL-22 Gets to the Stem of Colorectal Cancer, Immunity. 2014 May 15;40(5):639-41.
- Grivennikov SI. IL-11: A Prominent Pro-Tumorigenic Member of the IL-6 Family. Cancer Cell. 2013; (2):145-7.
- Francescone R, Hou V, Grivennikov SI. Microbiome, Inflammation and Cancer. Cancer J. 2014 May-Jun;20(3):181-9. Review.
- Grivennikov SI, Wang K, Mucida D, Stewart CA, Schnabl B, Jauch D, Taniguchi K., Yu GY, Osterreicher CH, Hung KE, Datz C, Feng Y, Fearon ER, Oukka M, Tessarollo L, Coppola V, Yarovinsky F, Cheroutre H, Eckmann L, Trinchieri G, Karin M. Adenoma-linked barrier defects and microbial products drive IL-23/IL-17-mediated tumour growth. Nature 2012; 491(7423):254-8.
- Meng F, Wang K, Aoyama T, Grivennikov SI, Paik Y, Scholten D, Cong M, Iwaisako K, Liu X, Zhang M, Osterreicher CH, Stickel F, Ley K, Brenner DA, Kisseleva T. Interleukin-17 signaling in inflammatory, Kupffer cells, and hepatic stellate cells exacerbates liver fibrosis in mice. Gastroenterology 2012; 143(3):765-76.e1-3.
- Gaba A, Grivennikov SI, Do MV, Stumpo DJ, Blackshear PJ, Karin M., Cutting edge: IL-10-mediated tristetraprolin induction is part of a feedback loop that controls macrophage STAT3 activation and cytokine production. J Immunol 2012; 189(5):2089-93.