MECHANISM OF MYELOID-DERIVED SUPPRESSOR CELL ACCUMULATION IN CANCER AND SUSCEPTIBILITY TO REVERSAL BY SUNITINIB
作者： Jennifer Susan Ko
DOI:
关键词:
摘要: The anti-angiogenic drug sunitinib is a receptor tyrosine-kinase (RTK) inhibitor with significant, yet not curative, therapeutic impacts in metastatic renal cell carcinoma (mRCC). Sunitinib also an immunomodulator, potently reversing myeloid-derived suppressor (MDSC) accumulation and T-cell inhibition the peripheral blood even of non-responder RCC patients. We observed that similarly prevented massive MDSC restored normal function spleens tumor-bearing mice, when had negligible upon tumor progression itself. Both monocytic neutrophilic splenic were highly inhibitable by sunitinib. In contrast, bone marrow proved resistant to sunitinib, ambient remained suppressed these compartments. Proteomic analyses comparing compartments demonstrated GM-CSF predicted resistance, recombinant could confer resistance vitro. conditioning inhibited STAT3 promoted STAT5 activation, whereas other hematopoietic support factors preferentially preserved both activation susceptibility. conclude compartmentaldependent exposure may account for sunitinib’s regionalized impact host modulation, hypothesize ancillary strategies decrease such
参考文章(293)
Christopher J. Sweeney, George W. Sledge, Kathy D. Miller, Can tumor angiogenesis be inhibited without resistance? Mechanisms of Angiogenesis. pp. 95- 112 ,(2005) , 10.1007/3-7643-7311-3_7
Dave S.B. Hoon, Edward Okun, Harry Neuwirth, Donald L. Morton, Reiko F. Irie, Aberrant expression of gangliosides in human renal cell carcinomas The Journal of Urology. ,vol. 150, pp. 2013- 2018 ,(1993) , 10.1016/S0022-5347(17)35956-6
Karim Bennaceur, Jessica Alice Chapman, Jean-louis Touraine, Jacques Portoukalian, Immunosuppressive networks in the tumour environment and their effect in dendritic cells. Biochimica et Biophysica Acta. ,vol. 1795, pp. 16- 24 ,(2009) , 10.1016/J.BBCAN.2008.07.001
TW Kuijpers, AT Tool, CE van der Schoot, LA Ginsel, JJ Onderwater, D Roos, AJ Verhoeven, Membrane surface antigen expression on neutrophils: a reappraisal of the use of surface markers for neutrophil activation. Blood. ,vol. 78, pp. 1105- 1111 ,(1991) , 10.1182/BLOOD.V78.4.1105.BLOODJOURNAL7841105
Brian G. Barnett, Jens Rüter, Ilona Kryczek, Michael J. Brumlik, Pui Joan Cheng, Benjamin J. Daniel, George Coukos, Weiping Zou, Tyler J. Curiel, Regulatory T cells: a new frontier in cancer immunotherapy. Advances in Experimental Medicine and Biology. ,vol. 622, pp. 255- 260 ,(2008) , 10.1007/978-0-387-68969-2_20
Li Yang, David P. Carbone, Tumor-host immune interactions and dendritic cell dysfunction. Advances in Cancer Research. ,vol. 92, pp. 13- 27 ,(2004) , 10.1016/S0065-230X(04)92002-7
Robert L Ilaria Jr, Robert G Hawley, Richard A Van Etten, None, Dominant Negative Mutants Implicate STAT5 in Myeloid Cell Proliferation and Neutrophil Differentiation Blood. ,vol. 93, pp. 4154- 4166 ,(1999) , 10.1182/BLOOD.V93.12.4154
Rafael F. Duarte, David A. Frank, SCF and G-CSF lead to the synergistic induction of proliferation and gene expression through complementary signaling pathways. Blood. ,vol. 96, pp. 3422- 3430 ,(2000) , 10.1182/BLOOD.V96.10.3422.H8003422_3422_3430
Edith M. Janssen, Edward E. Lemmens, Tom Wolfe, Urs Christen, Matthias G. von Herrath, Stephen P. Schoenberger, CD4 + T cells are required for secondary expansion and memory in CD8 + T lymphocytes Nature. ,vol. 421, pp. 852- 856 ,(2003) , 10.1038/NATURE01441
Stephanie K. Bunt, Pratima Sinha, Virginia K. Clements, Jeff Leips, Suzanne Ostrand-Rosenberg, Inflammation Induces Myeloid-Derived Suppressor Cells that Facilitate Tumor Progression Journal of Immunology. ,vol. 176, pp. 284- 290 ,(2006) , 10.4049/JIMMUNOL.176.1.284