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. 2016 Oct;27(10):1953-8.
doi: 10.1093/annonc/mdw289. Epub 2016 Aug 8.

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

A S Mansfield  1 , M C Aubry  2 , J C Moser  3 , S M Harrington  4 , R S Dronca  5 , S S Park  6 , H Dong  4
Affiliations

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

A S Mansfield et al. Ann Oncol. 2016 Oct.

Abstract

Background: 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.

Experimental design: 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 χ(2) or Fisher's exact test were used for analysis.

Results: 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).

Conclusions: 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.

Keywords: PD-L1; heterogeneity; lung cancer; metastasis; tumor immunology.

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Figures

Figure 1.
Figure 1.
Representative figure of concordant PD-L1 expression between lesions.
Figure 2.
Figure 2.
Circos diagrams of tumor cell and immune cell PD-L1 expression between paired lesions.
Figure 3.
Figure 3.
Circos diagram of tumor microenvironment categorizations between paired lesions.
See this image and copyright information in PMC

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