Expression of PD-1/PD-L1 and PD-L2 in peripheral T-cells from non-small cell lung cancer patients
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Oscar Arrieta1,*, Edgar Montes-Servín1,*, Juan-Manuel Hernandez-Martinez1,2,*, Andrés F. Cardona3, Eibar Casas-Ruiz1, José C. Crispín4, Daniel Motola5, Diana Flores-Estrada1 and Lourdes Barrera1
1Functional Unit of Thoracic Oncology and Laboratory of Personalized Medicine, Instituto Nacional de Cancerología, Mexico City, Mexico
2CONACyT-Instituto Nacional de Cancerología, Mexico City, Mexico
3Clinical and Translational Oncology Group, Institute of Oncology, Clínica del Country, Bogotá, Colombia
4Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
5Centro Oncológico, Hospital Médica Sur, Mexico City, Mexico
*These authors have contributed equally to this work
Oscar Arrieta, email: [email protected]
Keywords: immunotherapy; checkpoint inhibitors; lung adenocarcinoma; prognosis; circulating lymphocytes
Received: August 06, 2017 Accepted: September 03, 2017 Published: October 24, 2017
Binding of programmed death-1 (PD-1) with its ligands (PD-L1/2) transmits a co-inhibitory signal in activated T-cells that promotes T-cell exhaustion, leading to tumor immune evasion. The efficacy of antibodies targeting PD-1 and PD-L1 has led to a paradigm shift in lung cancer treatment but the prognostic and predictive value of tumor PD-L1 expression remains controversial. Evaluating PD-1, PD-L1/2 expression in peripheral blood cells may serve as a potential biomarker for prognosis and response to therapy. In this prospective observational study, plasma cytokine levels and PD-1, PD-L1 and PD-L2 expression was evaluated in circulating CD3+, CD3+CD4+ and CD3+CD8+ cells from 70 treatment-naïve patients with advanced NSCLC (Stage IIIB and IV) and from 10 healthy donors. The primary objective was to assess OS according to PD-1, PD-L1, PD-L2 expression status on PBMCs and lymphocyte subsets. Our results indicate that the percentage of PD-L1+CD3+, PD-L1+CD3+CD8+ PD-L2+PBMCs, PD-L2+CD3+, PD-L2+CD3+CD4+ cells was higher in patients than in healthy donors. Survival was decreased among patients with a high percentage of either PD-1+PBMCs, PD-1+CD3+, PD-L1+CD3+, PD-L1+CD3+CD8+, PD-L2+CD3+, PD-L2+CD3+CD4+, or PD-L2+CD3+CD8+ cells. IL-2 and TNF-α showed the strongest association with PD-L1 and PD-L2 expression on specific subsets of T-lymphocytes. Our findings suggest that increased PD-1/PD-L1/PDL-2 expression in PBMCs, particularly in T-cells, may be an additional mechanism leading to tumor escape from immune control. This study is registered with ClinicalTrials.gov, number NCT02758314.
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