Levels Of MDSC, Treg And Ts In Peripheral Blood And Their Clinical Significance In Cancer Patients

Part Ⅰ Level and clinical significance of MDSC in peripheral blood in cancer patients after different regimensObjectives To investigate the frequency and clinical significance of Myeloid-derived suppressor cells(MDSC) in peripheral blood of cancer patients after different treatment regimens.Methods Peripheral blood of 60 cancer patients and 10 healthy adults were collected in The Second Clinical College of Zheng Zhou University. Flow Cytometry was employed to determine the levels of CD14-CD11b~+CD33~+CD15~+MDSC(G-MDSC) and CD14~+CD11b~+MDSC(M-MDSC).Results(1) The baseline levels of G-MDSC and M-MDSC in cancer patients were significantly higher than those in healthy controls(P<0.05). The frequency ofG-MDSC was higher than that of M-MDSC in patients(P<0.05).(2) The level of M-MDSC was significantly higher than that of G-MDSC in peripheral blood of healthy people(P <0.05).(3) The baseline levels of G-MDSC and M-MDSC in gastrointestinal carcinomas patients were significantly higher than those in healthy controls(P<0.05), and the proportion of G-MDSC was higher than that of M-MDSC in patients(P<0.05).(4) Compared with other types of tumors, the baseline level of G-MDSC was significantly higher in gastrointestinal carcinomas patients(P<0.05), and the baseline level of M-MDSC was also higher than in these patients, but no statistical difference(P>0.05).(5) The dynamic changes of G-MDSC and M-MDSC were observed in peripheral blood of cancer patients after different cycle of chemotherapy. After the first cycle of chemotherapy, G-MDSC and M-MDSC levels were significantly lower than those before chemotherapy(P<0.05). The levels of two subsets of MDSC were reduced after the second cycle of chemotherapy in peripheral blood compared with those after the first cycle of chemotherapy in cancer patients, but no statistical difference(P>0.05). Compared with cancer patients after the second cycle of chemotherapy, the proportion of G-MDSC was significantly reduced after the third cycle of chemotherapy in peripheral blood of cancer patients(P<0.05). Level of M-MDSC was also reduced, but no statistical difference(P>0.05).(6) After operation, the level of M-MDSC was significantly reduced in peripheral blood of cancer patients(P<0.05). Level of G-MDSC was declined in peripheral blood of cancer patients, but no statistical difference(P>0.05).(7) Compared with pre-treatment, the proportion of G-MDSC was significantly reduced after surgery followed with chemotherapy(P<0.05). The level of M-MDSC was declined in peripheral blood of cancer patients, but no statistical difference(P>0.05).(8) Compared with combination therapy, chemotherapy reduced the levels of G-MDSC and M-MDSC more significantly in peripheral blood of cancer patients(P<0.05). Compared with the surgery, chemotherapy reduced the proportion of G-MDSC more significantly in peripheral blood of cancer patients(P<0.05). G-MDSC and M-MDSC levels had no significant difference between surgery and combination therapy in peripheral blood of cancer patients(P>0.05).(9) The level of G-MDSC was positively correlated with tumor diameter in peripheral blood of cancer patients(P<0.05), and M-MDSC level was negatively correlated with the histological grade(P<0.05).G-MDSC and M-MDSC levels were not correlated with age, gender, clinical stage, lymph node metastasis and pathological type(P> 0.05).Conclusions 1. The level of M-MDSC was significantly higher than that of G-MDSC in peripheral blood of healthy people. The proportions of two subsets of MDSC in peripheral blood of cancer patients were significantly up-regulated, and the frequency of G-MDSC was higher than that of M-MDSC in cancer patients. 2. The proportions of two subsets of MDSC in the peripheral blood of gastrointestinal cancer patients were significantly up-regulated than healthy peoples, and the frequency of G-MDSC was also higher than that of M-MDSC in cancer patients. 3. Surgery, chemotherapy, and their combination could reduce the level of G-MDSC or M-MDSC in peripheral blood of cancer patients, and chemotherapy can better reduce the levels of two subsets of MDSC. 4. With the increase of chemotherapy cycle in cancer patients, the levels of two subgroups of MDSC in cancer patients declined gradually. However, the levels of M-MDSC and G-MDSC at all time points after chemotherapy in patients were higher than those in healthy controls except for the M-MDSC level after the second cycle of chemotherapy. 5. The proportion of G-MDSC in peripheral blood of cancer patients was correlated with tumor diameters and tumor types, and M-MDSC was correlated with the histological grades.Part Ⅱ Monitoring levels of MDSC, Treg and Ts in Cancer Patients after DC-CIK immunotherapyObjectives To explore the changes of MDSC, Treg, Ts and Lymphocyte subsets levels in peripheral blood of cancer patients after DC-CIK immunotherapy.Methods Ninety six cases of cancer patients, accepted DC-CIK immunotherapy were enrolled. Levels of Treg, Ts and Lymphocyte subsets in peripheral blood of all cancer patients before and after immunotherapy were detected by FACS. Among them, the levels of two subsets of MDSC in 16 cases were detected after treatment by FACS.Results(1) Compared with pre-treatment, patients showed significantly higher percentage of CTL and lower level of Ts in peripheral blood after DC-CIK immunotherapy(P<0.05). No significant difference was found for Treg levels before and after treatment.(2) Compared with pre-treatment, gastrointestinal carcinomas patients showed lower percentage of Ts, and higher level CTL and Treg in peripheral blood after DC-CIK immunotherapy, but no statistical difference(P>0.05).(3) After DC-CIK Immunotherapy, the levels of CD3~+, CD3~+CD8~+, CD3~+CD4~+, and the ratio of CD4~+/CD8~+ in peripheral blood were significantly higher than those before treatment(P<0.05).(4) After DC-CIK Immunotherapy, the levels of CD3~+and CD3~+CD8~+in peripheral blood of gastrointestinal carcinomas patients were significantly higher than those before treatment(P<0.05). Levels of CD3~+CD4~+and the ratio of CD4~+/CD8~+in peripheral blood were higher than those before treatment, but no statistical difference(P>0.05).(5) The baseline levels of G-MDSC and M-MDSC in cancer patients were significantly higher than those in healthy controls(P<0.05). The proportion of G-MDSC was significantly reduced after DC-CIK immunotherapy(P<0.05). Level of M-MDSC was declined, but no statistical difference compared with baseline(P>0.05).(6) After treatment, the high level of Treg in peripheral blood of cancer patients after DC-CIK Immunotherapy was positively correlated with M-MDSC and negatively related to G-MDSC(P<0.05).(7) According to ir RC criteria, the effective rate was 6.25%, and disease control rate was 61.25%.Conclusions 1. DC-CIK immunotherapy can significantly reduce the levels of G-MDSC and Ts in peripheral blood of cancer patients. 2. The high level of Treg in peripheral blood of cancer patients after DC-CIK immunotherapy was correlated with M-MDSC. 3. DC-CIK immunotherapy can significantly improve levels of CTL, CD3~+C4~+T cells, and the ratio of CD4~+/CD8~+ in peripheral blood of cancer patients.