My research effort is directed toward defining the mechanisms by which the tumor microenvironment can negatively influence the development of T cell immunity to cancer. The major focus has been on T cell suppression mechanisms in patients with renal cell carcinoma (RCC). One main project has been to identify those gangliosides that are shed from human RCC and assess their impact on T cell function, including their capacity to modulate cytokine/chemokine gene expression and stimulate T cell apoptosis. Over the past 5 years the role of myeloid derived suppressor cells (MDSCs) in immune dysfunction has become the major focus in my laboratory. We showed that MDSCs were increased in the peripheral blood of RCC patients, and that in vitro depletion of these cells significantly reversed T cell suppression. We also showed that the tyrosine kinase inhibitor (TKI) sunitinib, which is now front line therapy for metastatic RCC, reduces the number of MDSCs in RCC patients and in 4 mouse tumor models, resulting in improved T cell function. We are beginning to define the mechanisms by which sunitinib inhibits MDSC accumulation in tumor bearing hosts, and to test whether the ability of sunitinib to restore T cell responses will improve immunotherapeutic outcomes when combined with vaccines or adoptive T cell therapy.
In other words ...
- Assessing the immunosuppressive and proangiogenic activity of MDSC in human tumors
- Determine how typosine kinease Inhibitors (TKI) impair MDSC function and survival
- Define the role of MDSC in resistant to TKI therapy
Jin Sub Kim M.S.
Senior Research Technologist
Paul Pavicic M.S.
Lead Research Technologist
Patricia A. Rayman M.S.
Principal Research Technologist
Charles S. Tannenbaum Ph.D.
Raychaudhuri B, Rayman P, Ireland J, Ko J, Rini BI, Borden E, Garcia J, Vogelbaum MA, and Finke J. 2011 Myeloid derived suppressor cell accumulation and function in newly diagnosed glioblastoma patients. Neuro-Oncology, In Press
Bose A, Taylor JL, Alber S, Watkins SC, Garcia JA, Rini, BI, Ko JS, Cohen PA, Finke JH
and Storkus WJ. 2010 Sunitinib facilitates the activation and recruitment of therapeutic anti-tumor immunity in concert with specific vaccination
. International Journal Cancer, 2010 Dec 17 [Epub ahead of print]
Ko JS, Zea AH, Rini BI, Ireland JL, Elson P, Cohen P, Golshayan A, Rayman P, Wood L, Garcia J, Dreicer R, Bukowski R and Finke JH
. 2009. Sunitinib Mediates Reversal of Myeloid-Derived suppressor Cell Accumulation in Renal Cell Carcinoma Patients
. Clinical Cancer Research, Clinical Cancer Research, 15(6):2148-2157
, Rini B, Ireland J, Rayman P, Richmond A, Golshayan A, Wood L, Elson P, Garcia J, Dreicer R, Bukowski R. 2008 Sunitinib reverses type-1 immune suppression and decreases T-regulatory cells in renal cell carcinoma patients.
Clin Cancer Res. Oct 15;14(20):6674-82.
Biswas K, Richmond A, Rayman P, Biswas S, Thornton M, Sa G, Das T, Zhang R, Chahlavi A, Tannenbrum CS, Novick A, Bukowski R and Finke JH. GM2 expression in renal cell carcinoma: Potential role in tumor-induced T-cell dysfunction.
Cancer Res 2006 66: 6816-6825.