Dynamic Change Of Regulatory T Lymphocytes And Regulatory B Lymphocytes After Chemotherapy In Patients With Advanced-Stage Lung Cancer

Part I Analysis of clinic-pathologic characteristics of advanced-stage lung cancer and prognostic factorsObjectives In order to better categorize patients with advanced-stage lung cancer into different subgroups, which is the basis for personalized therapy, this study analyzed the clinic-pathologic characteristics of advanced-stage lung cancer patients, as well as the prognostic factors.Methods Recruit study subjects, including advanced-stage lung cancer patients receiving first-line chemotherapy as the study group, and AECOPD patients, lung cancer high-risk people, and healthy volunteers as control groups; Collect clinical information including histological type, TNM stage, levels of serum tumor markers, regimens of first-line chemotherapy, the results of 1st time effectiveness assessment and so on; Follow up the subjects of study every three months to get the survival information.Results A total number of 36 patients with advanced-stage lung cancer and 6 patients with AECOPD,6 healthy people with high-risk for lung cancer, and 12 healthy volunteers were recruited in this study. More than 50% of male lung cancer patients were current smokers, while none of female lung cancer patients were current smokers or former smokers. The histological types of lung cancer were different in male and female. All female in this study had adenocarcinoma, while all squamous cell carcinoma and SCLC in this study occurred in male. Lung cancer, even in advanced stage, always manifests no symptoms or nonspecific symptoms, which makes early diagnosis difficult. About 50% of advanced-stage lung cancer patients in this study presenting cough as their first symptom. The time duration between onset of symptoms and the confirm diagnosis varies from 0.5 month to 60 months with median time of 1.8 months. This may also partly be explained by the nonspecific symptoms of lung cancer. Regular screening test might help detect lung cancer in an earlier stage, as were the four cases in this study. Also, combined serum tumor markers are more sensitive in detecting lung cancer compared with single serum tumor marker (88.6% vs 65.6%). After two cycles of first-line chemotherapy,80.5% of patients (29/36) were evaluated as SD or PR in the 1st effectiveness assessment by CT scan. Serum tumor markers increased in all patients evaluated as PD or Death, while serum tumor markers decreased in most patients evaluated as SD or PR. The median survival time of advanced-stage lung cancer patients receiving first-line chemotherapy was 17 months. No smoking history, NSCLC and SD or PR in the 1st effectiveness assessment by CT scan are good prognostic factors of advanced-stage lung cancer.Conclusions Smoking remains the main risk factor for lung cancer, especially for male patients. There are gender differences in lung cancer histology. Regular screening might help early detect lung cancer. Dynamic change of serum tumor markers before and after chemotherapy helps predict the effectiveness of first-line chemotherapy. No smoking history, NSCLC, and SD or PR in the 1st time effectiveness assessment by CT scan are good prognostic factors of advanced-stage lung cancer.Part II Dynamic change of regulatory T and regulatory B lymphocytes after chemotherapy in patients with advanced-stage lung cancerObjectives In order to provide theoretical support for possible chemotherapy combining with immunotherapy, we analyzed the characteristics of CD4 (+) CD25 (+) CD 127 (low) Tregs and CD 19 (+) IL-10 (+) Bregs in peripheral blood of advanced-stage lung cancer patients, the dynamic change of Tregs and Bregs before and after first-line chemotherapy, and its relationship with lung cancer prognosis.Methods Recruitment of subjects of study has been described in the first part. Briefly, study group of patients with advanced-stage lung cancer, control groups including AECOPD patients, lung cancer high-risk people, and healthy volunteers were recruited. Peripheral blood was taken before the 1st,2nd,3rd cycle of first-line chemotherapy in lung cancer patients. In control groups, peripheral blood was taken once. Then, peripheral blood mononuclear cells were separated using red blood cell lysis buffer. Finally, Tregs and Bregs were detected by flow cytometry. Levels of Tregs and Bregs were recorded as Tregs percentage in CD4 (+) T lymphocytes and Bregs percentage in CD 19 (+) B lymphocytes respectively. The clinic-pathologic information was the same as that in the first part.Results A total number of 36 patients with advanced-stage lung cancer and 6 patients with AECOPD,6 healthy people with high-risk for lung cancer, and 12 healthy volunteers were recruited in this study. Tregs percentage was increased in advanced-stage lung cancer patients compared with high risk people (3.37% vs 2.30%). There was no difference in Tregs percentage between lung cancer patients, AECOPD patients and healthy people. Bregs percentage in lung cancer patients was significantly higher than healthy volunteers (1.22% vs 0.05%), but was significantly lower than high risk people (1.22% vs 3.46%). After 1st cycle of first-line chemotherapy, peripheral Tregs pencentage was significantly decreased (3.37% vs 2.42%), however, after 2nd cycle of chemotherapy, Tregs percentage was slightly increased, which was still lower than that of the baseline. There was insignificant variation of Bregs percentage before and after chemotherapy. Tregs percentage and Bregs percentage was higher in lung cancer patients with longer survival time than in lung cancer patients with shorter survival time. Kaplan-Meier survival curve also showed that lung cancer patients with decreased Tregs after 1st cycle of first-line chemotherapy had better prognosis.Conclusions Peripheral Bregs percentage was increased in advanced-stage lung cancer patients compared with healthy volunteers. Peripheral Tregs percentage was significantly decreased after first-line chemotherapy. The dynamic change of peripheral Tregs percentage was related with lung cancer prognosis.