Study On Prognosis Of Small Cell Lung Cancer Based On Tumor Immune Microenvironment

Objective:In recent decades,the incidence of small cell lung cancer?SCLC?and its proportion in lung cancer in European and American countries have gradually decreased^[1,2],while those in lung cancer in China have gradually increased^[2-4].SCLC has a high degree of malignancy,but no significant progression was observed in treatment during the past 30 years^[5].Through the regulation of immune checkpoints?PD-L1and CTLA-4,etc.?,the normal human immune system can not only control and eliminate diseases but protect normal tissues from damage.In tumor patients,the change of tumor immune microenvironment may induce the expression of PD-L1ligand on the tumor cell surface,which combined with PD-1 and starts the brake of the body's immune function,finally lifts the body's immune response by making the T cells can not identify cancer cells and reduce T cells themselves proliferation or apoptosis.The purpose of this study is to explore the expression of checkpoint proteins in SCLC tumor immune microenvironment and its relationship with the prognosis of patients.Methods:Our study retrospectively collected the tumor wax mass tissues and clinical information of SCLC patients who underwent surgical resection and were confirmed as SCLC by postoperative pathology,and then make the microarray chips of SCLC tumor tissues.Finally,clinical and survival data of patients were combined with the IHC results for analysis using the SPSS 24.0 statistical software.Results:1.In the tumor microenvironment of SCLC patients,The survival time of patients with positive tumor infiltrating lymphocytes was significantly better than that of patients with negative tumor infiltrating lymphocytes.CD8 positive or FoxP3 positive on lymphocyte membrane surface was defined as tumor infiltrating lymphocyte?TILs?positive.In TILs positive group and negative group,the 1-year OS,PFS and LRFS of patients in the TILs positive and negative groups were:79.6%vs.50%?P=0.037?,64%vs.43.8%?P=0.079?,71.5%vs.50%?P=0.070?,respectively.2.In the tumor microenvironment of SCLC patients,The expression of PD-L1 on the surface of tumor cell membrane and immune cell membrane is positively correlated with the prognosis.The IHC results showed that the expression rate,location and prognosis of PD-L1were significantly different.The positive rate of PD-L1 expression on the surface of tumor cell membrane and the immune cell membrane was 49.3%?37 patients?,The1-year OS,PFS and LRFS in the positive group and the negative group were 80.8%vs.62.3%?P=0.054?,64%vs.49.6%?P=0.077?,78.1%vs.51.7%?P=0.035?.3.The expressions of immune checkpoint proteins in SCLC patients is positively correlated with prognosis.The positive of immune checkpoint protein was defined as PD-L1 positive?CPS score?or CTLA-4 positive.The negative of immune checkpoint protein was defined as PD-L1 negative?CPS score?and CTLA-4 negative.The 1-year OS,PFS and LRFS of patients in the positive immune checkpoint protein group and negative group were:80.6%vs.50.8%?P=0.010?,63.3%vs.39%?P=0.053?,74.2%vs.42.9%?P=0.017?,respectively.4.The relationship between the expression of TGF-?1 expression on fibroblast cell membrane and the prognosis of SCLC patients.The patients were divided into two groups:TGF-?1 high expression group and TGF-?1 low expression group.The 1-year OS,PFS and LRFS of patients in the high expression group and the low expression group were 79.4%vs.61.3%?P=0.004?,76.2%vs.35.4%?P=0.002?,78.6%vs.48.4%?P=0.004?,respectively.5.In SCLC patients with positive immune checkpoint protein,High expression of TGF-?1 on fibroblasts indicated a better prognosis of patients.Among the immune checkpoint protein positive group,the 1-year OS,PFS and LRFS of the patients with high TGF-?1 expression on the fibroblast membrane surface and low TGF-?1 expression group were 84.8%vs.61.4%?P=0.001?,80.2%vs.22.5%?P=0.000?,and 84.8%vs.22.5%?P=0.000?,respectively.Conclusion:The expression level of TGF-?1 on the fibroblast membrane surface in the tumor matrix of SCLC patients can be used as an independent biomarker to predict the prognosis of patients,and this may be related to the immune response response in the tumor microenvironment.However,Basic experiments and large surgical specimens are still needed to further explore.