Concordance of PD-L1 expression and CD8+ TIL intensity between NSCLC and synchronous brain metastases.

Sebnem Batur,Asli Cakir,Ebru Tastekin,Rengin Ahiskali,Sermin Durak,Onur Dulger,Hale Basak Caglar,Suheyla Bozkurt,Emine Bozkurtlar,Rashad Rzazade,Perran Fulden Yumuk,Buge Oz,Irfan Cicin

doi:10.17305/bjbms.2019.4474

Abstract

Programmed death-ligand 1 (PD-L1) is suggested to be a predictive biomarker in non-small-cell lung carcinoma (NSCLC). However, the differential expression of PD-L1 in primary lung tumor vs. synchronous metastases, especially brain metastasis (BM), remains unclear. This study assessed the concordance of PD-L1 expression on tumor cells and tumor-infiltrating lymphocytes (TILs) and CD8+ TIL intensity between primary lung tumors and synchronous BMs from 24 NSCLC patients. PD-L1, CD3, and CD8 positivity was determined by immunohistochemistry (IHC). PD-L1 scoring was based on the proportion of tumor cells with membranous expression of PD-L1 and the cutoff values <1%, 1–49%, and ≥50%. CD3 and CD8 positivity in TILs was evaluated semi-quantitatively and the proportion of CD3+/CD8+ TILs was determined. PD-L1 expression on tumor cells and TILs was evaluated in relation to CD3+/CD8+ TIL proportions and the intensity of CD8+ TILs between the paired primary lung and BM tissues. In the primary lung tumors, PD-L1 positivity was observed in 25%, 37.5%, and 37.5% cases for the cutoff values <1%, 1–49%, and ≥50%, respectively. PD-L1 expression on tumor cells was strongly correlated between the paired primary lung and BM tissues, in all cutoff groups. However, PD-L1 expression on TILs and the proportion of CD3+/CD8+ TILs were not strongly correlated in all three groups between the paired primary lung tumors and BMs. The intensity of CD8+ TILs was concordant in only 54.16% of the paired primary lung tumors and BMs. This study showed a high concordance of PD-L1 expression in neoplastic cells between primary NSCLC and synchronous BMs.

Highlights

Immunotherapies targeting the programmed cell death protein 1 (PD-1) and/or programmed death-ligand 1 (PD-L1) are relatively new and promising cancer therapeutic options
PD-L1 expression on tumor cells was statistically comparable between primary lung tumors and brain metastasis (BM), indicating that the concordance of PD-L1 expression on neoplastic cells between primary non-small-cell lung carcinoma (NSCLC) and their synchronous BMs is high
This means that the evaluation of PD-L1 in either primary lung tumor or BM can be considered valid in the selection of anti-PD-1/PD-L1 immunotherapy for patients

Summary

INTRODUCTION

Immunotherapies targeting the programmed cell death protein 1 (PD-1) and/or programmed death-ligand 1 (PD-L1) are relatively new and promising cancer therapeutic options. Even when stereotactic radiosurgery is an option, some tumors are just too large to be effectively managed by radiotherapy, and classical surgery remains as the only option This is important because, in many cases, the tissue removed from the brain is used as a biopsy material for various pathological analyses, including the determination of PD-1 and PD-L1 expression. In this sense, determining the concordance in PD-1 and/or PD-L1 expression between primary lung tumor and BM is important to be able to accurately determine the suitability of patient for immunotherapy [17]. This study assessed the concordance of PD-L1 expression on tumor cells and TILs and CD8+ TIL intensity between primary lung tumors and synchronous BMs from 24 NSCLC patients

MATERIALS AND METHODS

RESULTS

DISCUSSION