Temporal and spatial discordance of programmed cell death-ligand 1 expression and lymphocyte tumor infiltration between paired primary lesions and brain metastases in lung cancer

• Published in: Annals of oncology Vol. 27; no. 10; pp. 1953 - 1958
• Main Authors: Mansfield, A.S., Aubry, M.C., Moser, J.C., Harrington, S.M., Dronca, R.S., Park, S.S., Dong, H.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.10.2016; Oxford University Press
• Subjects: Adult; Aged; B7-H1 Antigen - genetics; Biomarkers, Tumor - genetics; Brain Neoplasms - genetics; Brain Neoplasms - pathology; Brain Neoplasms - secondary; CD3 Complex - genetics; Clinical Decision-Making; Female; Gene Expression Regulation, Neoplastic; heterogeneity; Humans; lung cancer; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Lymphocytes, Tumor-Infiltrating - metabolism; Lymphocytes, Tumor-Infiltrating - pathology; Male; metastasis; Middle Aged; Original; PD-L1; Programmed Cell Death 1 Receptor - genetics; tumor immunology; Tumor Microenvironment - genetics; lung cancer; PD-L1; tumor immunology; metastasis; heterogeneity
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/annonc/mdw289

The dynamics of PD-L1 expression may limit its use as a tissue-based predictive biomarker. We sought to expand our understanding of the dynamics of PD-L1 expression and tumor-infiltrating lymphocytes (TILs) in patients with lung cancer-related brain metastases. Paired primary lung cancers and brain metastases were identified and assessed for PD-L1 and CD3 expression by immunohistochemistry. Lesions with 5% or greater PD-L1 expression were considered positive. Agreement statistics and the χ2 or Fisher's exact test were used for analysis. We analyzed 146 paired lesions from 73 cases. There was disagreement of tumor cell PD-L1 expression in 10 cases (14%, κ = 0.71), and disagreement of TIL PD-L1 expression in 19 cases (26%, κ = 0.38). Most paired lesions with discordant tumor cell expression of PD-L1 were obtained 6 or more months apart. When specimens were categorized using a proposed tumor microenvironment categorization scheme based on PD-L1 expression and TILs, there were significant changes in the classifications because many of the brain metastases lacked either PD-L1 expression, tumor lymphocyte infiltration or both even when they were present in the primary lung cancer specimens (P = 0.009). We identified that there are significant differences between the tumor microenvironment of paired primary lung cancers and brain metastases. When physicians decide to treat patients with lung cancer with a PD-1 or PD-L1 inhibitor, they must do so in the context of the spatial and temporal heterogeneity of the tumor microenvironment.