CD8+ PD-1+ T-cells and PD-L1+ circulating tumor cells in chemotherapy-naïve non-small cell lung cancer: towards their clinical relevance?

Athanasios Kotsakis; Galatea Kallergi; Despoina Aggouraki; Zaharoula Lyristi; Filippos Koinis; Eleni Lagoudaki; Anastasios Koutsopoulos; Vassilis Georgoulias; Eleni-Kyriaki Vetsika

doi:10.1177/1758835919853193

CD8⁺ PD-1⁺ T-cells and PD-L1⁺ circulating tumor cells in chemotherapy-naïve non-small cell lung cancer: towards their clinical relevance?

Ther Adv Med Oncol. 2019 Jun 12:11:1758835919853193. doi: 10.1177/1758835919853193. eCollection 2019.

Authors

Athanasios Kotsakis¹, Galatea Kallergi², Despoina Aggouraki³, Zaharoula Lyristi², Filippos Koinis⁴, Eleni Lagoudaki³, Anastasios Koutsopoulos³, Vassilis Georgoulias², Eleni-Kyriaki Vetsika⁵

Affiliations

¹ School of Medical Sciences, University of Thessaly, GR-41334, Larissa, Thessaly, Greece.
² Laboratory Tumor Cell Biology, University of Crete, Medical School, Heraklion, Crete, Greece.
³ Hellenic Society of Immuno-Oncology, Athens, Greece.
⁴ Department of Medical Oncology, University General Hospital of Larissa, Thessaly, Greece.
⁵ School of Medical Sciences, University of Thessaly, Larissa, Thessaly, Greece.

Abstract

Background: Since tumor cells may escape from immune surveillance through the programmed cell death 1 (PD-1)/programmed death ligand (PD-L)1 axis, this study was designed in order to evaluate whether there is a correlation between the levels of PD-1⁺ and PD-L1⁺-expressing immune cells (ICs) and circulating tumor cells (CTCs) in patients with non-small cell lung cancer (NSCLC).

Patients and methods: Peripheral blood was obtained from 37 chemotherapy-naïve patients with metastatic NSCLC before treatment. PD-1 and PD-L1 expression was evaluated (1) on ICs with anti-tumor function (CD4⁺ and CD8⁺ T-cells, B-cells, monocytes/dendritic cells) using flow cytometry, (2) on CTCs by immunofluorescence and (3) on cells from tumor tissues by immunohistochemistry. The levels of PD-1⁺ and PD-L1⁺-expressing ICs were correlated with progression-free survival (PFS).

Results: The presence of PD-1⁺ CD8⁺ cells, with reduced interferon (IFN)-γ expression, but not other ICs, were positively correlated with PD-L1⁺ CTCs (p < 0.04). Increased percentages of PD-1⁺ CD8⁺ T-cells, were associated with a worse response to treatment (p = 0.032) and shorter PFS (p = 0.023) which, in multivariate analysis, was revealed as an independent predictor for decreased PFS [hazard ratio (HR): 4.1, p = 0.0007].

Conclusion: The results of the current study, for first time, provide evidence for a possible interaction between ICs and CTCs in NSCLC patients via the PD-1/PD-L1 axis and strongly support that the levels of PD-1⁺ CD8⁺ in these patients may be of clinical relevance.

Keywords: PD-1; PD-L1; circulating tumor cells; immune cells; immunosuppression.