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

Abstract

The tumor microenvironments of paired primary lung cancers and brain metastases are significantly different, such that many of the metastases lose PD-L1 expression, lymphocyte infiltration or both with greater discrepancies over time. The spatial and temporal heterogeneity of PD-L1 expression may limit its use as a tissue-based predictive biomarker in lung cancer.

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.

Journal

Journal ID (nlm-ta): Ann Oncol

Journal ID (iso-abbrev): Ann. Oncol

Journal ID (publisher-id): annonc

Journal ID (hwp): annonc

Title: Annals of Oncology

Publisher: Oxford University Press

ISSN (Print): 0923-7534

ISSN (Electronic): 1569-8041

Publication date (Print): October 2016

Publication date (Electronic): 08 August 2016

Publication date PMC-release: 08 August 2016

Volume: 27

Issue: 10

Pages: 1953-1958

Affiliations

[1 ]Division of Medical Oncology, Departments of Oncology

[2 ]Laboratory Medicine and Pathology

[3 ]Internal Medicine

[4 ]Urology

[5 ]Immunology

[6 ]Radiation Oncology, Mayo Clinic , Rochester, USA

Author notes

[* ] Correspondence to: Dr Aaron S. Mansfield, Division of Medical Oncology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. E-mail: mansfield.aaron@ 123456mayo.edu

Article

Publisher ID: mdw289

DOI: 10.1093/annonc/mdw289

PMC ID: 5035793

PubMed ID: 27502709

Copyright statement: © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology.

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact [e-mail]

Product

Funding

Funded by: National Institutes of Health;

Award ID: K12CA090628

Categories

Subject: Original Articles

Subject: Onco-Immunology