Nejat K. Egilmez, Ph.D.
Nejat K. Egilmez, Ph.D.
P.h.D., 1986, State University of New York at Buffalo
Department of Microbiology & Immunology
Voice (502) 852-5351
We are interested in studying the role of the immune system in tumor eradication versus progression with the long-term goal of developing immune-based therapies for cancer.
It is well-known that the tumor microenvironment is highly immune suppressive. In the past decade our studies demonstrated that local sustained delivery of TH1-promoting adjuvants to tumors can reverse tumor immune suppression and activate both local and systemic antitumor T-effector cell responses leading to eradication of disseminated disease. However, recent work revealed that such responses are transient. Further experiments identified the critical role of homeostatic regulatory mechanisms involving the IFNg - IDO+ tolerogenic Dendritic cell – T-regulatory cell axis in the premature termination of treatment-induced antitumor cytotoxic responses. We are currently delineating the molecular mechanisms that initiate and maintain post-therapy regulatory rebound.
Whereas acute activation of cytotoxic lymphocytes can result in tumor kill, myeloid cells that are found in chronic inflammatory environments can promote tumor growth. To this end, our group recently began investigating the therapeutic potential of oral immune adjuvants with tolerogenic properties in models of inflammation-driven polyposis and cancer. These studies have demonstrated that oral particulate formulations of Interleukin-10 can ameliorate both local and systemic disease via specific effects on intestinal CD4+ Foxp3+ RORgt+ IL-17+ pathogenic T-regulatory cells in a genetic murine model of intestinal polyposis. We are now evaluating this concept in a spontaneous colon cancer model and delineating the cellular mechanisms underlying the observed effects.
Chung AY, Li Q, Blair SJ, De Jesus M, Dennis KL, LeVea C, Yao J, Sun Y, Conway TF, Virtuoso LP, Battaglia NG, Furtado S, Mathiowitz E, Mantis NJ, Khazaie K, Egilmez NK. Oral Interleukin-10 Alleviates Polyposis via Neutralization of Pathogenic T-Regulatory Cells. Cancer Res. 2014 Oct 1;74(19):5377-85
Gerber SA, Lim JY, Connolly KA, Sedlacek AL, Barlow ML, Murphy SP, Egilmez NK, Lord EM. 2013. Radio-responsive tumors exhibit greater intratumoral immune activity than non-responsive tumors. Int J Cancer. E publication Nov 23.
Liu Y, Egilmez NK, Russell MW. 2013. Enhancement of Adaptive Immunity to Neisseria gonorrhoeae by Local Intravaginal Administration of Microencapsulated Interleukin 12. J Infect Dis. 208(11):1821-9.
Liu W, Baker SS, Trinidad J, Burlingame AL, Baker RD, Forte JG, Virtuoso LP, Egilmez NK, Zhu L. 2013. Inhibition of lysosomal enzyme activities by proton pump inhibitors. J Gastroenterol.
Manjili MH, Egilmez N, Knutson KL, Selvan SR, Ostberg JR. 2012. Tumor escape and progression under immune pressure. Clin Dev Immunol vol 2012; 1-2.
Egilmez NK, Harden JL, Rowswell-Turner RB. 2012. Chemoimmunotherapy as long-term maintenance therapy for cancer. Oncoimmunology. Jul 1;1(4):563-565.
Harden JL,Egilmez NK. 2012. Indoleamine 2,3-dioxygenase and dendritic cell tolerogenicity. Immunol Invest 41(6-7):738-64.
Virtuoso LP, Harden JL, Sotomayor P, Sigurdson WJ, Yoshimura F, Egilmez NK, Minev B, Kilinc MO. 2012. Characterization of iNOS+ Neutrophil-like ring cell in tumor-bearing mice. J Transl Med. 10(1):152
Rowswell-Turner RB, Nair RE and Egilmez NK. 2011. Chronic chemoimmunotherapy achieves cure of spontaneous murine mammary tumors via persistent blockade of post-therapy counter-regulation. J. Immunol. 187(8):4109-18.
Harden JL, Gu T, Kilinc MO, Rowswell-Turner RB, Virtuoso LP and Egilmez NK. 2011. Dichotomous effects of IFNg on Dendritic cell function determine the extent of Interleukin-12-driven antitumor T-cell immunity. J Immunol. 187(1):126-32.
Egilmez NK, Harden JL, Virtuoso LP, Schwendener R and Kilinc MO. 2011. Nitric Oxide Short-circuits Interleukin-12-mediated Tumor Progression. Cancer Immunol Immunother. 60(6):839-845.