Programmed cell death ligand-1 (PD-L1) expression combined with CD8 tumor infiltrating lymphocytes density in non-small cell lung cancer patients.

Cancer immunotherapy targeting programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) pathway has shown promising results in treatment of non-small cell lung cancer (NSCLC) patients. T cells play a major role in tumor-associated immune response. This study aimed to investigate PD-L1 expression alone and combined with CD8 tumor infiltrating lymphocytes (TILs) density in relation to clinicopathologic parameters and survival in NSCLC patients. Immunohistochemical analysis was used to evaluate PD-L1 expression and CD8 TILs density in 55 NSCLC patients. PD-L1 immunopositivity was detected in 36 (65.5%) of NSCLC cases. PD-L1 expression was significantly related to high tumor grade (p value = 0.038) and low CD8 TILs density (p value = 0.004), whereas no significant relations were detected between PD-L1 expression and tumor stage (p value = 0.121), overall survival (OS) (p value = 0.428) and progression-free survival (PFS) (p value = 0.439). Among PD-L1/CD8 TILs density groups, PD-L1+/CD8Low group was significantly associated with high tumor grade compared to PD-L1-/CD8high group (pairwise p = 0.016). PD-L1+/CD8Low group was significantly related to advanced tumor stage compared to PD-L1+/CD8high and PD-L1-/CD8Low groups (pairwise p = 0.001 and 0.013 respectively). PD-L1-/CD8high group exhibited the best OS and PFS whereas PD-L1+/CD8low group had the poorest OS and PFS (p value = 0.032 and 0.001 respectively). Assessment of PD-L1 combined with CD8 TILs density, instead of PD-L1 alone, suggested important prognostic relevance in NSCLC patients.

El-Guindy DM ，Helal DS ，Sabry NM ，Abo El-Nasr M ... -  《-》

Dynamic changes in PD-L1 expression and CD8(+) T cell infiltration in non-small cell lung cancer following chemoradiation therapy.

The treatment for stage III non-small cell lung cancer (NSCLC) is quite variable because stage III NSCLC is a heterogenous disease. Programmed death ligand 1 (PD-L1) and CD8+ tumor infiltrating lymphocytes (TILs) are thought to be related to treatment outcome in many tumors. To improve treatment outcome in stage III NSCLC, it is necessary to obtain data on PD-L1 expression and CD8+ TIL counts following CCRT and their relationship to treatment outcome. We retrospectively enrolled 43 patients with stage III NSCLC treated with neoadjuvant CCRT followed by surgery at Yonsei Cancer Center Severance Hospital in Korea between June 2008 and October 2010. PD-L1 level and CD8+ TIL numbers in tumors following CCRT were analyzed by immunohistochemistry, and their association with patient survival was evaluated with Kaplan-Meier method. More than half patients (52%) showed up- or downregulation of PD-L1 expression, and most patients (81%) showed change in CD8+ TIL counts by CCRT. Patients with PD-L1 expression following CCRT tended to have shorter recurrence free survival (RFS) (P = 0.182) or overall survival (OS) (P = 0.215) compared to the ones without PD-L1 expression. In the survival analysis with pre-CCRT specimens, neither RFS nor OS showed statistically significant differences. Patients with increased CD8+ TIL counts following CCRT regardless of pathological response strongly showed longer OS (median: not reached vs. 14.2 months for others; P = 0.017). CCRT dynamically alters PD-L1 expression and CD8+ TIL numbers in stage III NSCLC. Our data provide a rationale for combining CCRT and immunotherapy for the treatment of potentially resectable NSCLC.

Choe EA ，Cha YJ ，Kim JH ，Pyo KH ，Hong MH ，Park SY ，Shim HS ，Jung I ，Lee CY ，Cho BC ，Kim HR ... -  《-》

Prognostic value of PD-L1 expression in combination with CD8(+) TILs density in patients with surgically resected non-small cell lung cancer.

To investigate the prognostic value of PD-L1 expression combined with CD8+ TILs density in patients with resected NSCLC and correlations with clinicopathological features. We retrospectively enrolled 178 patients with resected NSCLC from 2011 to 2015. All surgical primary and 58 matched metastatic lymph node specimens were tested for PD-L1, CD8+ TILs, and oncogenic alterations. PD-L1+ was detected in 71 (39.9%) and CD8high TILs in 74 (41.6%) cases. Smoking, SqCC, and EGFR- were associated with both PD-L1+ and CD8high TILs. Patients with CD8high TILs had longer OS (P = 0.012). PD-L1- was significantly associated with longer OS in patients with oncogenic alterations (P = 0.047). By multivariate analysis, CD8high TILs (HR = 0.411; 95% CI, 0.177-0.954; P = 0.038), rather than PD-L1, was the independent predictive factor for OS. The longest and shortest OS were achieved in patients with PD-L1+ /CD8high and PD-L1+ /CD8low , respectively (P = 0.025). Inconsistent PD-L1 expression levels were observed in 23 of 58 (39.7%) patients with primary and matched metastatic lymph node specimens. Of them, CD8high TILs was significantly associated with longer OS in patients with metastatic lymph nodes and/or consistent PD-L1 expression (P = 0.017 and 0.049, respectively). The combination of PD-L1 and CD8+ TILs density, instead of PD-L1 alone, suggested impressive prognostic values in NSCLC patients. Less than half of patients with resected NSCLC experienced inconsistent PD-L1 expression between primary and metastatic lesions. The level of PD-L1 expression in advanced NSCLC needs to be evaluated more comprehensively.

Yang H ，Shi J ，Lin D ，Li X ，Zhao C ，Wang Q ，Zhang L ，Jiang T ，Zhao S ，Liu X ，Jia Y ，Zhang Y ，Cai W ，Zhou C ... -  《Cancer Medicine》

Prognostic Significance of Programmed Cell Death Ligand 1 (PD-L1), CD8+ Tumor-Infiltrating Lymphocytes and p53 in Non-Small Cell Lung Cancer: An Immunohistochemical Study.

Rashed HE ，Abdelrahman AE ，Abdelgawad M ，Balata S ，Shabrawy ME ... -  《-》

Predictive relevance of PD-L1 expression combined with CD8+ TIL density in stage III non-small cell lung cancer patients receiving concurrent chemoradiotherapy.

Expression of programmed cell death-ligand 1 (PD-L1) is known to be a mechanism whereby cancer can escape immune surveillance, but little is known about factors predictive of efficacy in patients with locally advanced non-small cell lung cancer (NSCLC). We investigated the predictive relevance of PD-L1 expression and CD8+ tumour-infiltrating lymphocytes (TILs) density in patients with locally advanced NSCLC receiving concurrent chemoradiotherapy (CCRT). We retrospectively reviewed 74 consecutive patients with stage III NSCLC who had received CCRT. PD-L1 expression and CD8+ TIL density were evaluated by immunohistochemical analysis. Univariate and multivariate analyses demonstrated that CD8+ TIL density was an independent and significant predictive factor for progression-free survival (PFS) and OS, whereas PD-L1 expression was not correlated with PFS and OS. Sub-analysis revealed that the PD-L1+/CD8 low group had the shortest PFS (8.6 months, p = 0.02) and OS (13.9 months, p = 0.11), and that the PD-L1-/CD8 high group had the longest prognosis (median PFS and OS were not reached) by Kaplan-Meier curves of the four sub-groups. Among stage III NSCLC patients who received CCRT, there was a trend for poor survival in those who expressed PD-L1. Our analysis indicated that a combination of lack of PD-L1 expression and CD8+ TIL density was significantly associated with favourable survival in these patients. It is proposed that PD-L1 expression in combination with CD8+ TIL density could be a useful predictive biomarker in patients with stage III NSCLC.

Tokito T ，Azuma K ，Kawahara A ，Ishii H ，Yamada K ，Matsuo N ，Kinoshita T ，Mizukami N ，Ono H ，Kage M ，Hoshino T ... -  《-》