The Expression And Clinical Significance Of PD-1 And PD-L1 In The Pulmonary Carcinoid

Objective: Pulmonary carcinoid(PC)is a neuroendocrine tumor from the lungs.It's pathological type is divided into typical carcinoid(TC)and atypical carcinoid(AC),and the prognosis of the disease is closely associated with its pathological features.Currently Treatment of PC is surgery,but for non-resectable patients with ad vanced PC treatment is very limited.With the rapid development of new tumor immunotherapy represented by anti-PD-1 / PD-L1 target,immunotherapy has been shown to be significant in many human tumors.With the rise of the developing immunotherapy represented by the anti-PD-1 / PD-L1 target therapy,it has shown a significant effect in various human tumors,including non-small cell lung cancer(NSCLC).In this study,the expressions of programmed death 1(PD-1)and programmed death ligand-1(PD-L1)in PC cells were detected,and further analyzed the correlation between the expression and corresponding clinical physiological and pathologic features.The aim is to further explore the anti-PD-1 / PD-L1 immunotherapy in PC.Methods: 20 cases were diagnosed with PC in the Tianjin Medical University General Hospital of lung cancer surgery from 2008 to 2015,which tumor specimens were confirmed by the department of pathology.In the study,we followed the telephone interview and outpatient visits.The clinical characteristics of all patients were collected in the medical record department,including age,sex,smoking history,pathological type and clinical stage(using the seventh edition of TNM staging in 2009).The expressions of PD-1 and PD-L1 in 20 cases of PC paraffin-embedded tissue specimens were detected by immunohistochemistry.H-score of immunohistochemical staining(range,0-300)was employed to evaluate the expression of PD-1 and PD-L1 in the tumor tissues.PD-1/CD8 was detected by double staining in order to grasp the expression of PD-1 in lymphocytes of CD8-positive lymphocytes.We further analyzed the differences in PD-1 and PD-L1 expression in PC with different pathological grades and pathological stages.The data were analyzed by IBM's SPSS software(version 21).The correlation between the expression of each gene protein and clinical featureswas analyzed by chi-square test or Fish exact test.When P <0.05,the results were statistically significant.Results: 1.According to clinical features: A total of 20 patients were enrolled,15 cases were male patients,5 cases were female patients among PC patients which is median age of 48.5 years;11 patients had a history of smoking,9 patients had no history of smoking.And there were 11 cases of AC patients,including 5 cases with lymph node metastasis(5/11)and 5 cases underwent invasion of the superior vena cava.There were 9 cases of TC patients who is no lymph node metastasis or invasion of superior vena cava,other surrounding blood vessels and other surrounding tissue.2.In 20 cases of PC tissues,PD-1 expression was positive in 8 patients,whic h the positive expression rate was 40%(8/20).The positive expression rate of PD-1 in smoking patients was 63.64%(7/11),which was significantly higher than that in non-smoking patients(11.11%,1/9)(P=0.028).The positive expression of PD-1 was not significantly correlated with sex,age,pathological type,pathological stage and metastasis of PC patients(P>0.05).3.In 20 cases of PC tissues,PD-L1 expression was positive in 9 patients,whic h the positive expression rate was 45%(9/20).The positive expression rate of PD-L1 in smoking patients is 45.45%(5/11),which was similar to that of non-smokers(44.44%,4/9).There was no significant difference between the two groups(P>0.05).The positive expression of PD-L1 was not significantly correlated with sex,age,pathological type,pathological stage and metastasis of PC patients(P> 0.05).4.In 20 cases of PC tissues,12 patients had PD-1 or / and PD-L1 expression.Among them,5 patients had positive expression of PD-1 and PD-L1,the positive rate was 25%(5/20),3 patients had positive PD-1 expression and negative PD-L1 expression,4 patients had positive PD-L1 expression and negative PD-1 expression.The correlation between PD-1 and PD-L1 positive expression was analyzed using the Fish exact test(P = 0.362),the result was not statistically significant.Due to the limitation of clinical cases,it is recommended that future studies should increase the sample size.5.20 PC patients were followed up for 15 months to 96 months and the meanfollow-up was 48 months.Among them,1 case of advanced AC patients died in July due to brain metastases in July,the remaining 19 patients were alive,so the current data can not be analyzed with PD-1 / PD-L1 positive expression and prognosis.Conclusion: 1.In the group of pulmonary carcinoid,survival prognosis was good,more men than women;all ages might be the disease,This group of research data is consistent with PC clinical characteristics.2.The positive expression rate of PD-1 and PD-L1 in PC patients was about 40%,which is similar to that of lung cancer.3.The positive expression rate of PD-1 in the smoking patients was signifcantly higher than that in the nonsmoking patients.4.These results suggest that the positive expression of PD-1 and PD-L1 may be related to the occurrence and development of PC.Immunotherapy with anti-PD-1 and PD-L1 antibodies may be beneficial for PD-1 and PD-L1-positive PC patients.