We are modeling the myeloid suppression found in tumors by characterizing how peritoneal cavity (PerC) macrophages (Mϕs) suppress lymphocyte activation. Cultured PerC Mϕs suppress the proliferation of C57BL/6J T cells by iNOS catabolism of arginine. To make our model more relevant to in vivo biology we initiated studies of ovarian cancer in the PerC. The ID8 cell line (mouse ovarian surface epithelial cell carcinoma) forms ovarian tumors and hemorrhagic ascites 5 weeks following i.p. injection into intact, syngeneic C57BL/6J mice. We found cancer development was accelerated in IL10-/- mice and delayed in iNOS-/- mice indicative that inflammation plays a role in cancer progression. Assessing mice before the ovarian cancer was fully developed we observed a depletion of CD44hi T and CD11b+IgMhi B cells in the PerC. With disease progression B and T cell depletion also became evident in the spleen. Lymphocyte depletion in the PerC correlated with ID8 expansion and the emergence of CD11b+F4/80+Gr-1+CD80+ myeloid suppressor cells (MSCs); splenic MSCs were CD80-. It was interesting to observe that GITR+ T cells, naturally enriched in the PerC of healthy, normal mice, persisted during MSC emergence in both the spleen and PerC. We are investigating what triggers the selective death of these important lymphocyte subsets. These results reveal an additional, challenging aspect of the immune suppression characteristic of myeloid cell emergence during cancer development.
- Copyright © 2013 by The American Association of Immunologists, Inc.