Role of immature myeloid cells in mechanisms of immune evasion in cancer.
Tumor affects myelopoiesis by inhibiting the process of differentiation/maturation of antigen-presenting cells from their myeloid precursors and by stimulating an accumulation of immature myeloid cells in cancer patients and tumor-bearing mice. These immature myeloid cells can contribute greatly to tumor progression and promote tumor evasion from immune attack: i) by inhibiting development of adaptive immune responses against tumor in lymphoid organs; ii) by migrating into tumor site and differentiating there into highly immune suppressive tumor-associated macrophages. Immature myeloid cells and tumor-associated macrophages utilize different JAK/STAT signaling pathways and different mechanisms to control T cell responses, which include increased production of TGF-beta, reactive oxygen species, peroxynitrites, as well as enhanced L-arginine metabolism. Understanding of precise mechanisms, which tumors use to affect differentiation of APC from myeloid cell precursors and inhibit T cell responses, could help to develop new approaches for cancer therapy and substantially improve efficiency of existing cancer vaccination strategies.
Kusmartsev
Sergei
S
H. Lee Moffitt Cancer Center and Research Institute and The Department of Interdisciplinary Oncology, University of South Florida, MRC 2067, 12902 Magnolia Dr, Tampa, FL 33612, USA.
Gabrilovich
Dmitry I
DI
D000818:Animals; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D022423:Myeloid Cells / Q000166:cytology* / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology*; D019139:Tumor Escape / Q000276:immunology*