Faculty and Research
Nejat Egilmez, Ph.D.
Professor of Microbiology and Immunology
Department of Microbiology and Immunology
138 Farber Hall
3435 Main Street
Buffalo, NY 14214
Tele: (716) 829-6059
Fax: (716) 829-2530
1986-1988, Postdoc, Louisiana St. Univ. Med. Ctr., New Orleans, LA
1986, Ph.D., State University of New York at Buffalo
1983, M.A., State University of New York at Buffalo
1980, Bachelor of Science, University of Minnesota, Minneapolis/St. Paul
Our primary area of interest is tumor immune suppression. More specifically we are investigating how tumors suppress anti-tumor immunity and whether this process can be reversed via the use of pro-inflammatory adjuvants and/or functional blocking/elimination of suppressive mechanisms. Our ultimate goal is to distill the information gathered from these studies to develop clinically effective tumor immunotherapy protocols.
Previous studies in our laboratory showed that intra-tumoral delivery of sustained-release cytokine (IL-2, IL-12, GM-CSF, TNFa) adjuvant formulations can result in the regression of established primary tumors, the development of systemic anti-tumor immunity and the eradication of metastatic disease in transplantable murine tumor models. Cellular/molecular analysis of post-therapy tumor microenvironment demonstrated that treatment induces the activation of a multi-component T-cell network including the rescue of pre-existing CD4+ and CD8+ T-effector/memory cells, the purge of T-suppressor cells and the priming of a de novo CD8+ cytotoxic T-effector cell response. More recent work exposed additional therapy-induced phenotypic/functional changes in tumor-associated NK cells and tolerogenic dendritic cells. We are currently investigating the mechanisms underlying the observed post-treatment changes in tumor-associated lymphocyte phenotype/function and the specific roles/interdependence of different lymphocyte subsets in tumor regression.Longer-term studies performed in the her-2/neu transgenic murine spontaneous mammary tumor model demonstrated that the reversal of immune suppression described above was transient and that intra-tumoral T-suppressor cells re-infiltrated tumors within 7 -10 days of treatment. Quantitative molecular/cellular monitoring of the tumor microenvironment demonstrated that repeated stimulation resulted in a progressive loss of anti-tumor efficacy and an intensification of the T-suppressor cell rebound after each treatment. Furthermore, we found that enhanced T-suppressor rebound was associated with a concomitant loss of tumor-specific CD8+ cytotoxic T-cells. We are now studying the mechanisms of post-therapy T-suppressor rebound and the accompanying loss of tumor-specific CTL. An extension of these studies involves the screening of various protocols that block T-suppressor activity in combination with therapy to determine whether long-term tumor cure can be achieved in her-2/neu transgenic mice.
Relevant references (1-6):
1. Egilmez, NK., Kilinc MO, Gu T and Conway TF. 2007. Controlled-release particulate cytokine adjuvants for cancer therapy. Endoc. Metabol. Imm. Dis. – Drug Targets 7(4):266-270.
2. Gu T, Kilinc MO and Egilmez NK. 2007. Transient activation of tumor-associated T-effector/memory cells promotes tumor eradication via NK-cell recruitment: Minimal role for long-term T-cell immunity in cure of metastatic disease. Cancer Immunol Immunother. Nov 30; [Epub ahead of print].
3. Watkins, SK, Egilmez, NK, Suttles, J and Stout RD. 2007. IL-12 rapidly alters the functional profile of tumor-associated and tumor-infiltrating macrophages in vitro and in vivo. J. Immunol.
4. Egilmez, NK. 2007. Cytokines as Vaccine Adjuvants. Vaccine Adjuvants and Delivery Systems, Manmohan Singh, ed. pp. J. Wiley & Sons, Hoboken, NJ, USA.
5. Kilinc, MO, Aulakh, KS, Nair RE, Jones SA, Alard, P, Kosiewicz, MM and Egilmez, NK. 2006. Reversing Tumor Immune Suppression with Intra-tumoral IL-12: Activation of Tumor-associated T-Effector/memory Cells, Induction of T-Suppressor Apoptosis and Infiltration of CD8+ T-Effectors. J. Immunol. 177(10):6962-73.
6. Nair RE, Kilinc MO, Jones SA and Egilmez, NK. 2006. Chronic immune therapy induces a progressive increase in intra-tumoral T-suppressor activity and a concurrent loss of tumor-specific CD8+ T-effectors in her-2/neu transgenic mice bearing advanced spontaneous tumors. J. Immunol. 176(12):7325-34.
7. Nair RE, Jong YS, Jones SA, Sharma A, Mathiowitz E and Egilmez, NK. 2006. IL-12 + GM-CSF Microsphere therapy induces eradication of advanced spontaneous tumors in Her-2/neu transgenic mice but fails to achieve long-term cure due to the inability to maintain effector T-cell activity. J Immunother 29(1):10-20.
Did you know?
Our faculty operates in state-of-the-art laboratories with easy access to core facilities, including genome sequencing; Affymetrix gene chip microarray stations; Laser scanning confocal and TIRF microscopy and robotic high through-put crystallization screening.
Conferences and Symposiums: