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

Edlund, Karolina ; Madjar, Katrin ; Mattsson, Johanna S.M. ; Djureinovic, Dijana ; Lindskog, Cecilia ; Brunnström, Hans LU orcid ; Koyi, Hirsh ; Brandén, Eva ; Jirström, Karin LU orcid and Pontén, Fredrik , et al. (2019) In Journal of Thoracic Oncology 14(4). p.628-640
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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Adenocarcinoma, Ki67, Lymphocyte, Prognosis, Squamous cell carcinoma
in
Journal of Thoracic Oncology
volume
14
issue
4
pages
628 - 640
publisher
Elsevier
external identifiers
  • scopus:85060939493
  • pmid:30639618
ISSN
1556-0864
DOI
10.1016/j.jtho.2018.12.022
language
English
LU publication?
yes
id
6f925739-ab04-4163-8c60-b5ee143bd648
date added to LUP
2019-02-13 11:07:12
date last changed
2024-06-11 04:40:20
@article{6f925739-ab04-4163-8c60-b5ee143bd648,
  abstract     = {{<p>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 &lt; 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.</p>}},
  author       = {{Edlund, Karolina and Madjar, Katrin and Mattsson, Johanna S.M. and Djureinovic, Dijana and Lindskog, Cecilia and Brunnström, Hans and Koyi, Hirsh and Brandén, Eva and Jirström, Karin and Pontén, Fredrik and Rahnenführer, Jörg and Micke, Patrick and Hengstler, Jan G.}},
  issn         = {{1556-0864}},
  keywords     = {{Adenocarcinoma; Ki67; Lymphocyte; Prognosis; Squamous cell carcinoma}},
  language     = {{eng}},
  month        = {{02}},
  number       = {{4}},
  pages        = {{628--640}},
  publisher    = {{Elsevier}},
  series       = {{Journal of Thoracic Oncology}},
  title        = {{Prognostic Impact of Tumor Cell Programmed Death Ligand 1 Expression and Immune Cell Infiltration in NSCLC}},
  url          = {{http://dx.doi.org/10.1016/j.jtho.2018.12.022}},
  doi          = {{10.1016/j.jtho.2018.12.022}},
  volume       = {{14}},
  year         = {{2019}},
}