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

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.

An analysis of the immunological tumor microenvironment of primary tumors and regional lymph nodes in squamous cell lung cancer

“…The PD-1/PD-L1 signaling pathway has been shown to transmit inhibitory signals to T lymphocytes and promote immune evasion of cancer cells (53). Batur et al reported that the concordance of the PD-L1 expression on cancer cells was high between primary NSCLCs and their synchronous brain metastases (54). According to our data, there was also significant concordance between the PD-L1 expression of cancer cells in primary tumors and lymph node metastases.…”

Discordance of immunotherapy response predictive biomarkers between primary lesions and paired metastases in tumours: A systematic review and meta-analysis

“…[22,27,28,39,40,44,52,53], four studies reported PD-L2[22,29,44,62], twelve studies reported TIL[20,29,30,43,46,[69][70][71][72][73][74][75], five studies reported TMB[23,30,[76][77][78], and six studies reported MSI status…”

Precision medicine biomarkers in brain metastases: applications, discordances, and obstacles

“…However, density of CD8+ TILs was concordant in only 54.16% of the paired primary lung tumors and BMs. 34 In terms of clinical efficacy, a large, multicenter retrospective analysis of NSCLC patients with new and/or growing BM without any previous local therapy reported similar intracranial (27.3%) and extracranial (22.7%) response rates with immune checkpoint inhibitor based treatment. 35 …”