Nitric Oxide-Independent CTL Suppression during Tumor Progression: Association with Arginase-Producing (M2) Myeloid Cells

作者：Yuanqing Liu, Jo A. Van Ginderachter, Lea Brys, Patrick DE BAETSELIER, Geert Raes, Anja B. Geldhof · 发表于：The Journal of Immunology · 年份：2003 · DOI：10.4049/jimmunol.170.10.5064 · 被引用次数：104 · 研究领域：Immune Cell Function and Interaction、Immune cells in cancer、Neutrophil, Myeloperoxidase and Oxidative Mechanisms

Most of the mice bearing a s.c. BW-Sp3 lymphoma tumor mount a CD8(+) T cell-mediated response resulting in tumor regression. Nonetheless, tumor progression occurs in some of the recipients and is associated with CTL inactivity. We demonstrated that T cell-activating APC were induced in regressors whereas T cell suppressive myeloid cells predominated in the spleen of progressors. Indeed, in vitro depletion of either the adherent or the CD11b(+) populations restored T cell cytotoxicity and proliferation in these mice. This CTL inhibition was cell-to-cell contact-dependent but not mediated by NO. However, the same progressor suppressive cells prevented the activity of in vitro-restimulated CTLs derived from regressors in a cell-to-cell contact and NO-dependent fashion. Thus, either the NO-dependent or -independent suppressive pathway prevailed, depending on the target CTL population. In addition, the suppressive population expressed a high arginase activity, suggesting an association of the suppressive phenotype with alternatively activated (M2) myeloid cells. However, the high arginase activity is not directly involved in the suppressive process. Our results provide new insights for myeloid cell-mediated CTL inhibition during cancer progression.