Prognostic Impact of Tumor Cell Programmed Death Ligand 1 Expression and Immune Cell Infiltration in NSCLC.

Abstract

INTRODUCTION:

Infiltration of T and B/plasma cells has been linked to NSCLC prognosis, but this has not been thoroughly investigated in relation to the expression of programmed death ligand 1 (PD-L1). Here, we determine the association of lymphocytes and PD-L1 with overall survival (OS) in two retrospective cohorts of operated NSCLC patients who were not treated with checkpoint inhibitors targeting the programmed death 1/PD-L1 axis. Moreover, we evaluate how PD-L1 positivity and clinicopathologic factors affect the prognostic association of lymphocytes.

METHODS:

Cluster of differentiation (CD) 3 (CD3)-, CD8-, CD4-, forkhead box P3 (FOXP3)-, CD20-, CD79A-, and immunoglobulin kappa constant (IGKC)-positive immune cells, and tumor PD-L1 positivity, were determined by immunohistochemistry on tissue microarrays (n = 705). Affymetrix data was analyzed for a patient subset, and supplemented with publicly available transcriptomics data (N = 1724). Associations with OS were assessed by Kaplan-Meier plots and uni- and multivariate Cox regression.

RESULTS:

Higher levels of T and B plasma cells were associated with longer OS (p = 0.004 and p < 0.001, for CD8 and IGKC, respectively). Highly proliferative tumors with few lymphocytes had the worst outcome. No association of PD-L1 positivity with OS was observed in a nonstratified patient population; however, a significant association with shorter OS was observed in never-smokers (p = 0.009 and p = 0.002, 5% and 50% cutoff). Lymphocyte infiltration was not associated with OS in PD-L1-positive tumors (50% cutoff). The prognostic association of lymphocyte infiltration also depended on the patients' smoking history and histologic subtype.

CONCLUSIONS:

Proliferation, PD-L1 status, smoking history, and histology should be considered if lymphocyte infiltration is to be used as a prognostic biomarker.

• Authors: Karolina Edlund, Katrin Madjar, Johanna S M Mattsson, Dijana Djureinovic, Cecilia Lindskog, Hans Brunnström, Hirsh Koyi, Eva Brandén, Karin Jirström, Fredrik Pontén, Jörg Rahnenführer, Patrick Micke, Jan G Hengstler
• Journal: Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer (J Thorac Oncol) Vol. 14 Issue 4 Pg. 628-640 (04 2019) ISSN: 1556-1380 [Electronic] United States
• PMID: 30639618 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Chemical References

• PDCD1 protein, human
• Programmed Cell Death 1 Receptor

Topics

• Aged
• Carcinoma, Non-Small-Cell Lung (genetics, immunology, pathology)
• Cohort Studies
• Female
• Humans
• Immunohistochemistry
• Lung Neoplasms (genetics, immunology, pathology)
• Lymphocytes, Tumor-Infiltrating (immunology, pathology)
• Male
• Prognosis
• Programmed Cell Death 1 Receptor (biosynthesis, genetics, immunology)
• Retrospective Studies
• Tissue Array Analysis