University of South Florida

Cancer Biology Ph.D. Program at the

Eduardo M. Sotomayor, M.D.

Associate Professor in the Department of Oncologic Sciences

Member-in-Residence of the Moffitt Cancer Center

E-mail: Eduardo.Sotomayor@moffitt.org
Phone: 813-745-1385

Training
M.D.: Federico Villarreal National, University School of Medicine; Lima, Peru, 1988.
Postdoctoral Fellow: Department of Microbiology and Immunology, University of Miami School of Medicine (Mentor: Diana M. Lopez Ph.D.), 1989-1992.
Internship: Jackson Memorial Medical Center, University of Miami School of Medicine (Internal Medicine), 1992-1993.
Residency: Jackson Memorial Medical Center, University of Miami School of Medicine (Internal Medicine), 1993-1995.
Fellowship in Oncology: Johns Hopkins Oncology Center (Mentor: Hyam Levitsky, M.D.), 1995-1998.

Research Interests
The immune system is well-equipped with cells that, when appropriately stimulated, can specifically recognize and kill cancer cells. However, as tumors expand a progressive impairment in the function of immune cells has been described. This impairment of T- cells negatively affects the ability of these cells to respond to immune-enhancing strategies currently used in the treatment of malignancies (i.e. vaccination with tumor-cell based vaccines). Indeed, studies in our laboratory have shown that early during tumor development (either hematologic malignancies or solid tumors), a critical subset of cells of the immune system (CD4+ T cells) are "paralyzed" or rendered tolerant. In other words, antigen-specific T-cells are still present in the tumor-bearing host but are unable to respond to stimulation that otherwise would lead to an effective activation of these cells.

Therefore, in our lab we have two major areas of interest:
a) To understand the cellular and molecular mechanism(s) involved in tolerance induction
In this regard, using parent-into-F1 bone marrow chimeras we have unambiguously demonstrated that tumor antigen processing and presentation by host's antigen-presenting cells or APCs (not tumor cell themselves) is the dominant mechanism underlying the development of antigen-specific T-cell tolerance. The requirement, therefore, for APCs in the induction of immune tolerance together with their well known role in priming effective T-cell responses, places APCs at the center of a critical decision leading to T-cell priming versus tolerance. More recently, we have identified that the JAK-STAT3 pathway in APCs may be playing a role in this critical decision.
b) Design strategies aimed to prevent and or revert this unresponsive state and therefore enhance the efficacy of the current generation of immunotherapeutic strategies.
We are currently exploring whether strategies designed to enhance APCs function (aminobisphosphonates) or strategies aimed to activate novel costimulatory pathways (CD40-CD40L; OX40R-OX40L; 4-1BBL/4-1BB) or to block inhibitory pathways (CTLA4 blockade; CD30-CD30L blockade) may prevent and or revert tumor induced antigen-specific T cell tolerance.

Search for publications by:   
This search will be conducted at the US National Library of Medicine (NLM) and PubMed.

Selected Publications
Sotomayor, E.M., Borrello, I., and Levitsky, H. Tolerance and Cancer: A critical issue in Tumor Immunology. Critical Reviews in Oncogenesis 7 (5): 433-456, 1996.

Sotomayor, E.M, Staveley-O’Carroll, K., Montgomery, J., Borrello, I., Hwang, L., Fein, S., Pardoll, D., and Levitsky, H. Induction of antigen-specific T cell anergy: An early event in the course of tumor progression. Proc. Natl. Acad. Sci. USA 95: 1178-1183, 1998.

Sotomayor E.M., I. Borrello, E. Tubb, F.Rattis, H. Bien, Zhengbin Lu, S. Fein, S.P. Schoenberger and Levitsky, H.I. Conversion of tumor-specific CD4 + T cell tolerance to T-cell priming through in vivo ligation of CD40. Nature Medicine 5: 780-787, 1999.

Sotomayor, E.M., Borrello, I., Tubb, E., Allison, J.P. and H. I Levitsky. CTLA-4 blockade in vivo enhances the priming of responsive T cells, but fails to prevent the induction of antigen-specific tolerance Proc. Natl. Acad. Sci. USA. 96:11476-11481,1999.

Antonia, S. and Sotomayor, E.M. Gene Therapy for lung cancer. Current Opinion in Oncology 12: 138-142, 2000.

Sotomayor E.M., I. Borrello, F-M. Rattis, Cuenca, A., J. Abrams, K. Staveley-O’Carroll, and Levitsky, H.I. Cross-presentation of tumor antigens by bone marrow derived antigen-presenting cells is the dominant mechanism in the induction of T-cell tolerance during B-cell lymphoma progression. Blood 98: 1070-1077, 2001.

Sotomayor, E.M., Piantadosi, S., Miller, C.B., Karp, J.E., Jones, R.J., Rowley, S.D., Kaufmann, S.H., Braine, H., Burke, P.J., and Gore, S. Long-term follow-up of intensive, ara-C-based chemotherapy followed by bone marrow transplantation for adult acute lymphoblastic leukemia : Impact of induction Ara-C dose and post-remission therapy. Leukemia Research 26(5):461-71, 2002.

Borrello, I. and Sotomayor, E.M. Cancer vaccines for hematologic malignancies. Cancer Control 9: 138-151, 2002.

Cheng, F., H. Wang, Cuenca, A., M. Huang, T. Ganshar, J. Brayer, W.G. Kerr, K. Takeda, S. Akira, S. Schoenberger, H. Yu, R. Jove, and Sotomayor, E.M. A critical role for Stat3 signaling in immune tolerance. Immunity 19:425-436, 2003.

Cuenca, A., Cheng, F., H. Wang, Brayer, J., Horna, P., Gu, L., Bien, H., Borrello, I., Levitsky, H.I. and Sotomayor, E.M. Extra-lymphatic solid tumor growth is not immunologically ignored and results in early induction of antigen-specific T cell tolerance: Dominant role of “cross-tolerance” to tumor antigens. Cancer Research 63:9007-9015, 2003.

Wang, H., Cheng, F., Cuenca, A., Horna, P., Zheng, Z., Bhalla, K. and Sotomayor, E.M. Imatinib Mesylate (STI-571) enhances antigen presenting cell function and overcomes tumor-induced CD4+ T-cell tolerance. Blood. First Edition Paper, Prepublished Online September 28, 2004.