Myeloid-derived suppressor cells and associated events in urethane-induced lung cancer

Abstract

OBJECTIVES:Myeloid-derived suppressor cells contribute to the immunosuppressive microenvironment during tumor development and limit the efficacy of cancer immunotherapy. Identifying myeloid-derived suppressor cells and associated factors is the first step in creating strategies to reverse the suppressive effects of these cells on the immune system.METHODS:To induce lung cancer, we administered 2 doses of urethane to BALB/c mice and observed these animals for 120 days. After this period, we evaluated the percentage of myeloid-derived suppressor cells in the blood, lung and bone marrow. The expression of alpha-smooth muscle actin, transforming growth factor-β, Toll-like receptor 2, Toll-like receptor 4, and interleukin-6 was also determined in the lung tissue.RESULTS:Myeloid-derived suppressor cells were increased in all evaluated tissues after lung cancer development in association with increased Toll-like receptor 4 expression and decreased interleukin-6 expression in the lung. We observed alpha-smooth muscle actin and transforming growth factor-β expression in lung nodules.CONCLUSIONS:We believe that the early diagnosis of cancer through determining the blood levels of myeloid-derived suppressor cells followed by the depletion of these cells should be further investigated as a possible approach for cancer treatment.

Impact of Endostatin Gene Therapy on Myeloid-Derived Suppressor Cells From a Metastatic Renal Cell Carcinoma

“…The tumor microenvironment is able to partially block the differentiation of IMC and, consequently, promote the expansion of immature cells in the bone marrow [10,12,15,33,34]. The data presented in this study demonstrated that CD11b + Gr-1 + cells, particularly the granulocytic subtype, were expanded in bone marrow, which corroborates data reported in the literature [35][36][37]. The lymphoid organ is described as a locale where PMN-MDSC cells mediate the antigen-specific suppressive mechanisms [12].…”

The paradoxical role of tumor-infiltrating immune cells in lung cancer

“…Tumors and their surrounding stroma can produce growth factors, cytokines, and chemokines that recruit, expand, and activate MDSCs. Teixeira and colleagues (44) noted an increased number of MDSCs infiltrating lung cancer in mice. Another study confirmed the hypothesis that activating immune cells through disruption of MDSC-mediated immune suppression would promote antitumor immunity in a murine model of lung cancer (45).…”

Alternative Chemotherapies: Angiotensin-Converting Enzyme Inhibitors Reduce Myeloid-Derived Suppressor Cells to Benefit Older Patients with Colorectal Cancer

“…The mechanism therefore is not clear, but may involve an effect of the drugs on MDSCs. Our group (VB and NMF) has investigated these cells in experimental models of lung cancer and in clinical cases of CRC [26][27][28][29][30]. In the urethane-induced lung cancer model, we found an increased percentage of infiltrating MDSC, high expression of ACE mRNA and protein in addition to intense expression of ACE protein in tumor nodules in the lungs [29].…”