P2.09-15 PD-L1 Expression and Lymphocyte Infiltration in Resected Stage IIIAN2 NSCLC: Preliminary Data from a Lung ART Ancillary Study

Abstract

Patients with resectable stage IIIA N2 NSCLC, are at high risk of both systemic and loco-regional relapse following surgical resection, necessitating neo-adjuvant or adjuvant treatments. Prognostic biological markers are needed. Parameters from the immune microenvironment, including PD-L1 expression and lymphocytic infiltration, have been poorly described in this group of patients. Thus we assessed simultaneously PD-L1 expression and TIL density in a cohort of stage IIIA N2 Lung ART patients, and correlated the results with clinical and pathological features before adjuvant treatment. Formalin fixed paraffin-embedded tumor surgical specimens from 247 patients included in the Lung Adjuvant Radiotherapy Trial (NCT00410683) were studied. PD-L1 immunohistochemistry was performed centrally on whole slides using a validated clinical PD-L1 assay. Expression of PD-L1 in tumor cells (TC) and immune cell (IC) was scored by a trained pathologist. Morphological assessment of TIL density (percentage of tumor area) was performed on whole hematoxylin-eosin stained slides. Surgical and pathology reports were reviewed by an independent expert committee for tumor staging. Association between immune parameters and baseline clinical characteristics were assessed in exploratory analyses in order to provide insights on immune activity in resected NSCLC patients. PD-L1 expression in ≥1% TC, ≥50% TC, ≥1% IC, ≥10% IC was observed in 47.8%, 21.9%, 61.5%, 7.3% of patients, respectively. In univariate analysis, high PD-L1 expression in both tumor cells and immune cells for all cut points correlated strongly with a higher TIL density (p-values ≤0.001). In 41 (16.6%) patients with preoperative chemotherapy (CT), a higher TIL density was observed (mean 28.1 vs. 17.5%, p=0.0018) as compared to patients without preoperative CT, but no difference was noted for PD-L1 expression in both TC and IC,. Skip N2 metastases were associated with a higher TIL infiltration (mean 22.9% vs. 17.4% p=0.014). We found no significant correlation between PD-L1 or TIL infiltration with the number of mediastinal lymph nodes stations involved on pathological examination and with histological tumor subtypes (squamous cell carcinoma vs. adenocarcinoma). PD-L1 expression levels in TC and IC appeared similar in stage IIIA N2 NSCLC as compared to other stages. Expression in both TC and IC strongly correlated with TIL infiltration, suggesting a prominently immune-induced expression mechanism. Preoperative chemotherapy was associated with a higher TIL infiltration but not higher PD-L1 expression. Patients with skip N2 metastases harbored a higher level of TIL density, a finding consistent with a more active immune microenvironment in this group of patients with better prognosis. These data will be subsequently updated on a larger number of patient and correlated to clinical follow-up.