Tumors develop a milieu that fosters their development and counteract the total efficacy of immune system through different mechanisms. TGF-β, a potent growth suppressor and immunosuppressive cytokine has the capacity to inhibit the anti-tumor immune response in several models. However, all the mechanisms underlying the effects of TGF-β are not well known. Specifically, the role of TGF-β in shaping the cancer microenvironment is ill-defined. Our objective is to characterize the role of TGF-β in shaping the neoplastic microenvironment using a leukemia model. Using the TGF-β producing EL4 cell line, we characterized the immune cell infiltration and the levels of several cytokines in the context of systemic TGF-β neutralization. When compared to tumor extracted from untreated animals, leukemic masses that had evolved in the context of TGF-β inhibition had increased levels of inflammatory cytokines and a tendency to accumulate more activated T cells and surprisingly more myeloid cells, unveiling a potential role for these cells in leukemia specific immunity. More precisely, secretion of cytokines involved in migration and activation of leucocytes, namely IL-2, GM-CSF, KC and MIP-1α was significantly induced in treated animals. Our data suggest that TGF-β blockade alters the leukemic microenvironment. Further studies will confirm the impact of TGF-β on the leukemic milieu including immune cells, stromal cells and angiogenesis and how this cytokine impedes anti-cancer immunity.
- Copyright © 2013 by The American Association of Immunologists, Inc.