Send to

Choose Destination
J Thorac Oncol. 2019 Apr;14(4):628-640. doi: 10.1016/j.jtho.2018.12.022. Epub 2019 Jan 9.

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

Author information

Leibniz Research Centre for Working Environment and Human Factors (IfADo) at TU Dortmund University, Dortmund, Germany. Electronic address:
Department of Statistics, TU Dortmund University, Dortmund, Germany.
Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Department of Clinical Sciences, Division of Oncology and Pathology, Lund University, Lund, Sweden.
Department of Respiratory Medicine, Gävle Hospital, Gävle, Sweden; Centre for Research and Development, Uppsala University/Region Gävleborg, Gävle, Sweden.
Leibniz Research Centre for Working Environment and Human Factors (IfADo) at TU Dortmund University, Dortmund, Germany.



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.


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.


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.


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


Adenocarcinoma; Ki67; Lymphocyte; Prognosis; Squamous cell carcinoma

Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center