Prognostic significance of PD-L1 expression and tumor infiltrating lymphocyte in surgically resectable non-small cell lung cancer

Abstract

Programmed death ligand 1 (PD-L1) expression is a predictive biomarker of the success of PD-1/PD-L1 inhibitor therapy for patients with advanced non-small cell lung cancer (NSCLC) but its role as a prognostic marker for early stage resectable NSCLC remains unclear. Here, we studied PD-L1 expression and tumor infiltrating lymphocytes (TILs) in surgically resectable NSCLC and correlate the finding with clinicopathological features and patient outcomes. Total of 170 archival samples of resectable NSCLC were probed for PD-L1 expression using the clone 22C3 pharmDx kit. The PD-L1 expression was determined by the Tumor Proportion Score (TPS) and classified into TPS <1%, TPS 1 to 49% and TPS ≥50%. The scoring of TILs was from hematoxylin & eosin stained tissue sections using a system for standardized evaluation of TILs in breast cancer. PD-L1 expression was compared with clinical pathological characteristics and survival outcome. Expression of PD-L1 scores of TPS ≥50%, TPS 1 to 49% and TPS <1% were observed in 10.6%, 24.7% and 64.7% of the 170 archival samples, respectively. Positive PD-L1 expression was significantly higher in patients with squamous carcinoma, in those with higher TNM stage and with the presence of TILs. Neither the PD-L1 expression, TIL status, nor their combination was an independent prognosis biomarker of survival when the data was subjected to either univariate or multivariate analysis. The incidence of PDL1 expression appears to be lower in patient with early stage resectable lung cancer. PD-L1 expression and TILs are not prognostic indicators of survival outcome in this population.

Prognostic Impact of Tumor Cell Programmed Death Ligand 1 Expression and Immune Cell Infiltration in NSCLC

“…It cannot be excluded that the lack of survival association in the PD-L1-positive subset is due to the smaller sample size, but our findings agree with the results of Tokito et al 41 who showed that the combination of high CD8-positive cell density and the absence of PD-L1 expression was associated with better outcome based on the analysis of 74 stage III NSCLC patients, as well as with findings by Koh et al 42 , who analyzed 497 primarily stage I NSCLCs and showed that PD-L1 negativity in combination with a low PD1/CD8 ratio was associated with longer disease-free survival. On the contrary, a combination of PD-L1 status and level of tumor infiltrating lymphocyte was not associated with survival in the analysis of 170 NSCLCs according to Lin et al 20 Our results support the conclusion that the presence of immune inhibitory factors should be taken into account if immune cell infiltration is to be considered a prognostic biomarker in NSCLC. Furthermore, additional modifying factors should be considered.…”

“…13 In this patient population, it has been reported that PD-L1 positivity is associated with better as well as worse outcome, or no association with outcome was observed. [14][15][16][17][18][19][20][21] Methodological differences, such as the use of different antibody clones, immunohistochemistry (IHC) protocols, and cutoffs for PD-L1 positivity is likely to contribute to these dissimilar findings, but they may also be due to differences in the distribution of demographic or clinicopathologic parameters in the evaluated patient cohorts, or to the levels of infiltrating immune cells in the corresponding tumors. In the present investigation, we aimed to (1) determine the association of lymphocyte infiltration and PD-L1 status with overall survival (OS), and (2) evaluate how PD-L1 positivity and clinicopathologic factors affect the prognostic association of lymphocyte infiltration in NSCLC patients not treated with PD-1/PD-L1 inhibitors.…”

Tumor-infiltrating T cells and PD-L1 expression in childhood malignant extracranial germ-cell tumors

“…[17][18][19][20] PD-L1 expression has been investigated in many malignancies, including breast, kidney, lung, esophagus, ovary, colorectal, head and neck, squamous cell carcinomas, melanomas, GISTs, gliomas and neuroblastoma. [21][22][23][24][25] Very little is known about the expression of PD-L1 and the density of TILs subsets in pediatric and adolescent malignant extracranial germ-cell tumors (meGCTs), a heterogeneous group of tumors representing 3-5% of all childhood cancers occurring before 15 years of age, and 15% of neoplasms in adolescents aged 15-19 years. 26,27 MeGCTs derive from primordial germ cells (PGC) and can occur both within and outside the gonads.…”

Programmed Death-Ligand 1 Expression in Non-Small Cell Lung Carcinoma Biopsies and Its Association with Tumor Infiltrating Lymphocytes and the Degree of Desmoplasia

“…riou PST ≥ 10 % (p = 0,008). To je v súlade s výsledkami viacerých autorov, ktorí upozorňujú na možnú asociáciu medzi expresiou PD-L1 v nádorových bunkách a infiltráciou nádorovej strómy T-lymfocytmi [15][16][17]. V skupine nízko diferencovaných, grade 3 adenokarcinómov patrilo 15 z 27 prípadov (55,5 %) do kategórie PST ≥ 50 %.…”