| Lung cancer is one of the most common malignant tumors, with high mortality rate worldwide, and still accounting for 1.3 million new cases annually. Of these, non-small cell lung cancer (NSCLC) accounts for approximately 85%. Despite the introduction of new chemotherapeutic agents and several molecularly targeted drugs in the past decade, the outcome of 5-year overall survival remain poor. At present, the research of T cells in anti-tumor effect has become a hot research at home and abroad. Significant progress in tumor immunotherapy has resulted in several new strategies for cancer therapy, including T-cell checkpoint inhibitors, chimeric antigen receptor T cells. And the domestic researches on tumor immune cell therapy have achieved rapid development since 2010. However, there are no clear indicators for tumor immune cell therapy, including the plan and timing of individual treatment, monitoring and evaluation of anti-tumor effect. The relationship between prognosis after immunotherapy and T lymphocyte subsets in patients is also unclear. Studies have shown that regulatory T cells (Tregs), involved in the formation of tumor immune tolerance and the inhibition of anti-tumor immune responses, is an important component of T lymphocyte subsets. Forhead/winged helix transcription factor (Foxp3) as a specific marker of Tregs has been demonstrated in many studies. Due to the expression of Foxp3 within Tregs, they must be fixed ruptured when quantitated, which makes operation complex and also bad for the subsequent functional studies. Therefore, it is not appropriate that Foxp3 is a marker of clinical popularization in detection of immune function. Recent studies show that CD 127 expression inversely correlates with Foxp3. On the one hand, CD127 is expressed on the cell surface, which thus is easy to be detected. On the other hand, staining will not cause damage to Tregs. Hence CD 127 can be used as a good biomarker for the identification and separation of human Tregs. In this study, we investigated variation in T lymphocyte subsets including Tregs in peripheral blood and their clinical significance in patients with advanced NSCLC, which will provide some basis for the clinical immunotherapy, prognosis prediction and screening for high-risk patients in clinical practice. Meanwhile, we will make a Meta-analysis by searching the relevant domestic and foreign published literatures. Based on data of a large sample, we can assess the association of T lymphocyte subsets including Tregs and prognosis in patients with NSCLC comprehensively, which will not only confirm the results of our clinical research, but also provide evidence-based decision-making for immunotherapy of lung cancer.Part I Detection and clinical significance of regulatory T cells in peripheral blood of patients with advanced non-small cell lung cancer[Objective] To discuss the correlation between the frequency of Tregs, natural killer T cells (NKT cells) and the ratio of CD4+/CD8+T cells in patients with advanced NSCLC before DC-CIK immunotherapy and prognosis.[Method] A total of 45 patients with advanced NSCLC were enrolled in the study. The relationship between Tregs, NKT cells and the ratio of CD4+/CD8+T cells with the clinicopathologic characteristics of patients was evaluated by Spearman analysis. The prognostic factors for advanced NSCLC patients were evaluated by Cox regression.[Results] The ratio of CD4+/CD8+T cells in peripheral blood after DC-CIK immunotherapy declined significantly. Tregs and NKT cells were related to the tumor size. The number of Tregs was also significantly correlated with the survival rate (P<0.05).[Conclusion] The frequency of Tregs in peripheral blood is an independent predictive factor for judging the prognosis of patients with advanced NSCLC. The result indicates that the level of CD4+CD25+Tregs with the specific cell surface marker GD127 in peripheral blood may help screening for high-risk patients, evaluating the immune state and prognosis, especially guiding the clinical immunotherapy.Part II A Meta analysis of regulatory T cells, CD4+and CD8+T lymphocytes and prognosis in NSCLC[Objective] We took out a Meta analysis to determine the prognostic value of Tregs in peripheral blood and stromal Foxp3+Tregs, stromal CD4+and CD8+T lymphocytes in NSCLC.[Method] An established literature search strategy for Pubmed, MEDLINE, Elsevier Science, CNKI, CNKI and other English and Chinese databases was designed. Literatures were included, in which the prognostic significance of Tregs in peripheral blood and stromal Foxp3+Tregs, stromal CD4+and CD8+T lymphocytes were determined in patients with NSCLC. We extracted and recorded the relevant results and then made quantitative assessment on these dates with Meta analysis methods, in which all analyses were carried out using the Meta-Analysis program of Stata software (version 12.0 for Windows, StataCorp LP, College Station, TX).[Results] Sixteen studies with a total 2791 patients with NSCLC were included for the analysis. Tregs in peripheral blood had a negative effect on overall survival (OS) with a hazard ratio (HR) of 1.99 (95% confidence interval (CI) 1.42-2.78). Similarly, stromal Foxp3+Tregs had a negative effect on OS with a HR of 2.04 (95%CI 1.60-2.61). Stromal Foxp3+Tregs were linked to relapse free survival (RFS), but the statistically significant HR value did not interpreted into obviously shortened RFS. Meanwhile, stromal CD4+and CD8+T lymphocytes had a positive effect on OS with a HR of 0.64 (95%CI 0.51-0.80) and 0.75 (95%CI 0.64-0.87) separately.[Conclusion] The FCM result of Tregs in peripheral blood and the IHC result of stromal Foxp3+Tregs, CD4+and CD8+T lymphocytes in NSCLC showed significantly correlation with the OS negatively or positively, respectively. The low frequency of Tregs in peripheral blood and the suppressed expression of stromal Foxp3+Tregs favored the OS separately. The overexpression of stromal CD4+and CD8+T lymphocytes favored the OS separately. The relationship between overexpression of stromal Foxp3+Tregs and RFS remained to be further confirmed. |
PDF Full Text Request