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Prognostic Impact of Tumor Cell Programmed Death Ligand 1 Expression and Immune Cell Infiltration in NSCLC
TU Dortmund Univ, Leibniz Res Ctr Working Environm & Human Factors, Dortmund, Germany.
TU Dortmund Univ, Dept Stat, Dortmund, Germany.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi. (Patrick Micke)ORCID-id: 0000-0002-5294-7808
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi. (Fredrik Pontén, Patrick Micke)
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2019 (engelsk)Inngår i: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 14, nr 4, s. 628-640, artikkel-id S1556-0864(19)30009-7Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

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.

sted, utgiver, år, opplag, sider
2019. Vol. 14, nr 4, s. 628-640, artikkel-id S1556-0864(19)30009-7
Emneord [en]
Adenocarcinoma, Ki67, Lymphocyte, Prognosis, Squamous cell carcinoma
HSV kategori
Forskningsprogram
Patologi
Identifikatorer
URN: urn:nbn:se:uu:diva-380592DOI: 10.1016/j.jtho.2018.12.022ISI: 000462167700021PubMedID: 30639618OAI: oai:DiVA.org:uu-380592DiVA, id: diva2:1300642
Forskningsfinansiär
Swedish Cancer Society, 15 0831Tilgjengelig fra: 2019-03-29 Laget: 2019-03-29 Sist oppdatert: 2020-01-03bibliografisk kontrollert

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Mattsson, Johanna Sofia MargaretaDjureinovic, DijanaLindskog, CeciliaKoyi, HirshBrandén, EvaPontén, FredrikMicke, Patrick

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