Clinical Application Study Of PD-L1/PD-1 In Non-small Cell Lung Cancer

Objectives: We found programmed death-1-ligand 1 (PD-L1) was a negative prognosis factor for patients with non-small cell lung cancer (NSCLC) for 3 years follow-up in our previous study. In order to further confirm our study result, we followed up 5 years and picked up some different patients with NSCLC underwent surgical resection in the same period in our hospital.Materials and methods: PD-L1 expression in 120 NSCLC tissue specimens and 10 benign control samples embedded with wax were detected by immunohistochemistry.Results: No PD-L1 expression was found in 10 benign controls, while 57.5% tissue specimens of NSCLC had PD-L1 expression. There was no relationship between PD-L1 expression and patient age, gender, histopathological type. However, PD-L1 expression was significantly correlated to the degree of tumor cell differentiation, local lymph node metastasis, stage of tumor-node-metastasis (TNM) and survival time of patients. Poor tumor cell differentiation, local lymph node metastasis, and advanced stage of TNM were related with higher PD-L1 expression. PD-L1 negative NSCLC patients had longer overall 5-year survival time compared with PD-L1 positive ones (P <0.001). PD-L1 status was a significant independent prognostic factor of NSCLC (x~2 = 18.153, RR = 2.946, P < 0.001). Conclusion: Up-regulated PD-L1 expression in NSCLC is related with the degree of tumor cell differentiation, local lymph node metastasis and stage of TNM. PD-L1 expression is an important risk factor associated with poor prognosis of NSCLC. Objectives: To explore the expression of PD-L1~+ (programmed death-1-ligand 1) CD68~+ macrophages and PD-1~+ (programmed death-1) CD3~+CD8~+CD28~+ T lymphocytes in peripheral blood mononuclear cells (PBMCs) of non-small cell lung cancer (NSCLC) by flow cytometry (FCM).Materials and methods: 60 squamous cell carcinoma patients, 60 adenocarcinoma patients and 60 healthy controls were recruited in the study. PD-L1~+CD68~+ macrophages and PD-1~+CD3~+CD8~+CD28~+ T lymphocytes were isolated from PBMCs of the 180 persons with FCM.Results: Squamous cell carcinoma and adenocarcinoma group had higher PD-L1~+CD68~+ macrophages expression compared to healthy controls (t = 5.112, P < 0.001 and t = 2.545, P = 0.013, respectively), and PD-L1~+CD68~+ macrophages from squamous cell carcinoma were higher than that from adenocarcinoma group [(19.03±12.28)% vs (14.21±11.88)%, P = 0.031)].Squamous cell carcinoma and adenocarcinoma group had higher PD-1~+CD3~+ CD8~+CD28~+ T lymphocytes expression compared to healthy controls (t = 3.587, P = 0.001 and t = 5.009, P < 0.001, respectively), and expression of PD-1~+CD3~+CD8~+CD28~+ T lymphocytes between squamous cell carcinoma group and adenocarcinoma group showed no statistical significance (t = 1.098,P = 0.275).Conclusions: PD-L1~+CD68~+ macrophages and PD-1~+CD3~+CD8~+CD28~+ T lymphocytes in PBMCs have marked relationship with squamous cell carcinoma and adenocarcinoma. PD-L1~+CD68~+ macrophages and PD-1~+CD3~+CD8~+CD28~+ T lymphocytes may play important roles in immune escape of NSCLC. Objectives: To evaluate the correlation between the polymorphisms of PD-L1 gene and the susceptibility of Non-small cell lung cancer (NSCLC) .Materials and methods: 293 NSCLC patients and 293 healthy controls enrolled in this study.PD-L1 intron 4 position 8923 A/C polymorphism was typed using the PCR-restriction fragment length polymorphism method. The interactions between genotype, A/C allele frequency and NSCLC susceptibility were also analyzed.Results: The A/C genotype frequencies were significantly different between NSCLC patients and controls. The AC frequencies were higher in NSCLC patients than in controls (13.3% vs 6.5%), The CC frequencies were higher in NSCLC patients than in controls too (3.4% vs 1.3%). The AA frequencies were lower in NSCLC patients than in controls (83.3% vs 92.2%). AC genotype plus CC genotype group had higher risk of NSCLC than AA group (OR = 2.357; 95%CI 1.395-3.984). C-allele frequency was higher in NSCLC patients than in controls (10.1% vs 4.6%), while the A-allele frequency was lower in NSCLC patients than in controls (89.9% vs 95.4%). More risk of NSCLC was found in the individuals who carried with C-allele than in those carried with A-allele (OR = 2.318; 95%CI 1.448-3.711).Conclusion: An A/C polymorphism at position 8923 in PD-L1 is associated with NSCLC. The PD-L1 Polymorphism plays a role in NSCLC development, especially in patients with the C allele or with CC/AC genotype at position 8923 in PD-L1 gene.