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*
H. Lee Moffitt Cancer Center, University of South Florida, Tampa, FL 33612; and
Cancer Immunology Program, Cardinal Bernardin Cancer Center, Loyola University of Chicago, Maywood, IL 60153
The mechanism of tumor-associated T cell dysfunction remains an unresolved problem of tumor immunology. Development of T cell defects in tumor-bearing hosts are often associated with increased production of immature myeloid cells. In tumor-bearing mice, these immature myeloid cells are represented by a population of Gr-1+ cells. In this study we investigated an effect of these cells on T cell function. Gr-1+ cells were isolated from MethA sarcoma or C3 tumor-bearing mice using cell sorting. These Gr-1+ cells expressed myeloid cell marker CD11b and MHC class I molecules, but they lacked expression of MHC class II molecules. Tumor-induced Gr-1+ cells did not affect T cell responses to Con A and to a peptide presented by MHC class II. In sharp contrast, Gr-1+ cells completely blocked T cell response to a peptide presented by MHC class I in vitro and in vivo. Block of the specific MHC class I molecules on the surface of Gr-1+ cells completely abrogated the observed effects of these cells. Thus, immature myeloid cells specifically inhibited CD8-mediated Ag-specific T cell response, but not CD4-mediated T cell response. Differentiation of Gr-1+ cells in the presence of growth factors and all-trans retinoic acid completely eliminated inhibitory potential of these cells. This may suggest a new approach to cancer treatment.
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B. Yu, S. Kusmartsev, F. Cheng, M. Paolini, Y. Nefedova, E. Sotomayor, and D. Gabrilovich Effective Combination of Chemotherapy and Dendritic Cell Administration for the Treatment of Advanced-Stage Experimental Breast Cancer Clin. Cancer Res., January 1, 2003; 9(1): 285 - 294. [Abstract] [Full Text] [PDF]
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V. Bronte, P. Serafini, C. De Santo, I. Marigo, V. Tosello, A. Mazzoni, D. M. Segal, C. Staib, M. Lowel, G. Sutter, et al. IL-4-Induced Arginase 1 Suppresses Alloreactive T Cells in Tumor-Bearing Mice J. Immunol., January 1, 2003; 170(1): 270 - 278. [Abstract] [Full Text] [PDF]
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A. B. Geldhof, J. A. Van Ginderachter, Y. Liu, W. Noel, G. Raes, and P. De Baetselier Antagonistic effect of NK cells on alternatively activated monocytes: a contribution of NK cells to CTL generation Blood, December 1, 2002; 100(12): 4049 - 4058. [Abstract] [Full Text] [PDF]
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D. I. Gabrilovich, P. Cheng, Y. Fan, B. Yu, E. Nikitina, A. Sirotkin, M. Shurin, T. Oyama, Y. Adachi, S. Nadaf, et al. H1{degrees} histone and differentiation of dendritic cells. A molecular target for tumor-derived factors J. Leukoc. Biol., August 1, 2002; 72(2): 285 - 296. [Abstract] [Full Text] [PDF]
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L. I. Terrazas, K. L. Walsh, D. Piskorska, E. McGuire, and D. A. Harn Jr. The Schistosome Oligosaccharide Lacto-N-neotetraose Expands Gr1+ Cells That Secrete Anti-inflammatory Cytokines and Inhibit Proliferation of Naive CD4+ Cells: A Potential Mechanism for Immune Polarization in Helminth Infections J. Immunol., November 1, 2001; 167(9): 5294 - 5303. [Abstract] [Full Text] [PDF]
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