Study On The Relationship Between The Characteristics Of Circulating T Lymphocytes And Prognosis In Patients With Small Cell Lung Cancer

Background ang Aim:Lymphocytes play an important role in tumor immunity,and lymphocyte-related immunotherapy has achieved remarkable results in recent years.At present,the research on tumor-related lymphocytes is mainly focused on tumor infiltrating lymphocytes,but there is still a lack of sufficient research and understanding on the characteristics and changes of peripheral blood lymphocytes in patients with cancer.Tumor microenvironment,especially inflammation-related responses,is important to the cancer development,and may be related to systemic inflammation.Small cell lung cancer accounts for 10%of lung cancer.It has strong invasiveness,rapid growth and poor prognosis.More and more evidence shows that immunotherapy has great potential in the therapy for SCLC.Some SCLC patients have immune response to tumor-associated antigens and have a good prognosis,but the characteristics of peripheral blood lymphocytes in patients with small cell lung cancer have not been reported.The purpose of this study was to investigate the partial characteristics of peripheral blood T lymphocytes in patients with extensive SCLC and to observe the correlation between T lymphocytes and the prognosis of patients with SCLCMethods:This study included 36 newly diagnosed patients with extensive stage SCLC patients from Shandong Cancer Hospital.In order to avoid the effect of radiotherapy and chemotherapy on peripheral blood lymphocytes,peripheral blood samples were taken before the patients received treatment,and the therapeutic efficacy and prognosis of the patients were followed up.All patients received standard treatment.At the same time,22 healthy volunteers matched with age and sex were selected,and peripheral blood samples were taken as control.T lymphocytes were isolated from peripheral blood with human peripheral blood lymphocyte separation medium,and the percentage of different lymphocyte subsets was determined by flow cytometry.CD4+T cells and CD8+T cells were separated by immunomagnetic beads and stained with carboxyfluorescein diacetate succinimidyl ester(CFSE)then cultured for 5 days.The ability of cell proliferation was detected by flow cytometry.The prognosis of the patients was followed up and the relationship between the prognosis and the characteristics of peripheral blood lymphocytes was analyzed.Results:CD4+CD25+Foxp3+ regulatory T cells were elevated in extensive stage SCLC patients compared with healthy controls(p=0.0083).In contrast,the percentages of CD3+and CD3+CD4+T cells were significantly lower in SCLC patients(p<0.001;p=0.0014).The proliferation(%divided)of CD8+T cells of SCLC patients was suppressed compared with healthy controls(p=0.0058),but not of CD4+T cells(p=0.1611).Multivariate analyses showed that the%divided of CD8+T cells is an independent predictor for PFS(HR:4.342,95%CI:1.324-14.245;p=0.015).The percentages of peripheral Tregs and the degree of chemotherapy or radiotherapy induced lymphopenia negatively correlated with the proliferation of CD8+T cells(p=0.0225,r=-0.379;p=0.0003,r=-0.464).Conclusion:The present study found that the SCLC patients had decreased proliferation ability of CD8+T cells,increased Tregs subsets and decreased CD3+and CD3+CD4+T cells subsets,suggesting that the whole immune function was impaired in SCLC patients.The proliferation potential of circulating CD8+T cells is a significant predicator for PFS.Patients with decreased proliferation ability suggest a poor prognosis.Further study on the mechanism of the decreased proliferation potential of circulating CD8+T cells may promote the development of immunotherapy for SCLC.