Evaluation of peripheral blood T lymphocyte surface activation markers and transcription factors in patients with early stage non-small cell lung cancer

•Dysregulation of immune system starts early during the development of NSCLC.•An elevated level of the CD4+FoxP3+ cells in PBMC of patients with early NSCLC.•Patients with early lung cancer present the aberrated PD-1 and CTLA-4 expression.•High peripheral level of CD4+PD-1+ cells as a poor prognosti...

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Veröffentlicht in:Cellular immunology 2017-12, Vol.322, p.26-33
Hauptverfasser: Rutkowski, Jacek, Cyman, Marta, Ślebioda, Tomasz, Bemben, Kamila, Rutkowska, Aleksandra, Gruchała, Marcin, Kmieć, Zbigniew, Pliszka, Agnieszka, Zaucha, Renata
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Sprache:eng
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Zusammenfassung:•Dysregulation of immune system starts early during the development of NSCLC.•An elevated level of the CD4+FoxP3+ cells in PBMC of patients with early NSCLC.•Patients with early lung cancer present the aberrated PD-1 and CTLA-4 expression.•High peripheral level of CD4+PD-1+ cells as a poor prognostic factor.•Patients with a high peripheral CD4+/CD8+ratio have longer overall survival. Lung cancer cells harboring multiple mutations as a consequence of long-term damage by different etiologic factors are responsible for high immunogenicity. Immune checkpoint inhibitors significantly improve treatment results in non-small cell lung cancer (NSCLC). Unfortunately, the role of T-lymphocytes in early NSCLC has not been sufficiently elucidated. The aim of this study was to characterize peripheral blood T cells expressing several selected surface antigens (CD4, CD8, CD25, CD28, PD-1, CTLA-4) and transcription factors (T-bet, ROR-yt, Fox-P3, GATA-3) in this patient population. The study group (LC) consisted of 80 treatment-naïve patients with T1/2aN0M0 NSCLC and was compared with 40 cancer-free patients matched for non-oncological diseases and demographic parameters (CG). Significantly higher counts of CTLA-4+cells (in both CD4+and CD8+subtypes), a lower proportion of PD-1 expressing cells and a significantly higher percentage of Fox-P3+CD4+cells were found in the LC group. The high proportion of CD4+PD-1+cells significantly correlated with poor outcomes in LC group, while low CD4/CD8 ratio predicted a better prognosis. Based on our results it seems that NSCLC even at early stages of development initiate changes in the proportions of T cells that may have a significant impact on the clinical outcome.
ISSN:0008-8749
1090-2163
DOI:10.1016/j.cellimm.2017.09.007