Immune alterations and M1/M2 shifting of monocytes in patients with non-small cell lung cancer

219 Lung cancer is a serious health issue worldwide due to its highest mortality rate among cancers and the poor responsiveness to present therapy. Immune aberrations have been reported to play a pivotal role in tumorogenesis and myeloid suppressor cells-mediated immune suppression has been demonstrated in animal models of tumor. Type 1 monocytes with a high expression of iNOS have an important function in the defense mechanism against tumor and a shift to type 2 monocytes with a low expression of iNOS may attenuate the anti-tumor activity. In the present study, we explored the immune alterations in the patients with non-small cell lung cancer. Peripheral blood mononuclear cells were isolated and flow cytometry was used to analyze the amount of myeloid suppressor cells (MSC, % of CD11b+/CD14- cells of non-monocytic PBMNC), monocytes (CD14/iNOS, M1/M2), helper cells/cytotoxic T cells (CD4/CD8), regulatory T cells (CD4/CD25/Foxp3), and NK cells (CD1d/Vα24). Data were expressed as mean±SEM, Kruskal-Wallis test and Mann-Whitney U test were used to analyze the difference between study subsets. Our preliminary data showed that the amount of myeloid suppressor cells was significantly increased in the treatment-naive patients, compared to the control subjects (31.26±6.12%, n=18 vs 9.36±1.93, n=8, p=0.0163). The M1/M2 ratio was ranged widely from 0.081 to 5.6 in patients, compared to a narrow range from 0.126 to 0.699 in control subjects. The CD4/CD8 ratio was significantly increased in patients (3.88±0.77, n=10 vs 0.98±0.05, n=6, p=0.0002) due to a significant decrease in CD8 cells (8.67±1.34%, n=10 vs 31.38±2.38%, n=6, p=0.0002). The amount of regulatory T cells was also increased in the cancer patients. Additionally, our data also showed a negative association between the population of MSC and the M1/M2 ratio of monocyte (r= -0.7527, p=0.003, n=13, Spearman test), suggesting a negatively modulatory interaction between the MSCs and monocytes. Our results revealed that there is an immune alteration in the patients with NSCLC. The molecular mechanism of the interaction between these cells and the clinical-therapeutic implication of the immune alteration are under study.