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Immunophenotype of T Cells Expressing Programmed Death-1 and Cytotoxic T Cell Antigen-4 in Early Lung Cancer: Local vs. Systemic Immune Response

1
Department of Internal Medicine and Hematology Laboratory of Flow Cytometry, Military Medical Institute, Warsaw, ul. Szaserow 128, 04-141 Warsaw, Poland
2
Laboratory of Flow Cytometry, Centre of Postgraduate Medical Education, ul. Marymoncka 99/103, 01-813 Warsaw, Poland
3
Department of Surgery, Institute of Tuberculosis and Lung Diseases, ul. Plocka 26, 01-138 Warsaw, Poland
4
Department of Pathology, Medical University of Warsaw, ul. Pawinskiego 7, 02-106 Warsaw, Poland
5
Department of Internal Medicine, Pulmonary Diseases and Allergy, Medical University of Warsaw, ul. Banacha 1a, 02-097 Warsaw, Poland
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(4), 567; https://doi.org/10.3390/cancers11040567
Received: 9 March 2019 / Revised: 11 April 2019 / Accepted: 19 April 2019 / Published: 21 April 2019
(This article belongs to the Special Issue Signaling Pathways and Immune Checkpoint Regulation in Cancer)
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Abstract

The overexpression of programmed death-1 (PD-1) and cytotoxic T cell antigen 4 (CTLA-4) receptors on T cells are among the major mechanisms of tumor immunoevasion. However, the expression pattern of these receptors on T cell subpopulations of a different activation status and at different sites is poorly characterized. Thus, we analyzed the expression of PD-1 and CTLA-4 on the naïve, activated, memory, and activated memory T cells. Bronchoalveolar lavage fluid (BALF) from the lung affected by lung cancer (clBALF), the opposite ‘healthy’ lung (hlBALF), and peripheral blood (PB) samples were collected from 32 patients. The cells were analyzed by multiparameter flow cytometry. The proportion of memory, activated, and activated memory CD8+ cells with the expression of PD-1 and CTLA-4 were elevated in the clBALF when compared to the hlBALF (insignificantly), but these proportions were significantly higher in the BALF when compared with the PB. The proportions of PD-1+ and CTLA-4+ T cells were elevated in the squamous cell carcinoma when compared to the adenocarcinoma patients. Also, the expression of PD-1 and CTLA-4 on T cells from the BALF was significantly higher than from PB. We report for the first time the differential expression of checkpoint molecules on CD4+ and CD8+ lymphocytes at a different stage of activation in the local environment of lung cancer. Moreover, the circulating T cells have a distinct expression of these receptors, which suggests their poor utility as biomarkers for immunotherapy. View Full-Text
Keywords: CTLA-4; cytotoxic T cell antigen 4; PD-1; programmed death-1; BALF; bronchoalveolar lavage fluid; lung cancer; immunotherapy CTLA-4; cytotoxic T cell antigen 4; PD-1; programmed death-1; BALF; bronchoalveolar lavage fluid; lung cancer; immunotherapy
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Kwiecien, I.; Skirecki, T.; Polubiec-Kownacka, M.; Raniszewska, A.; Domagala-Kulawik, J. Immunophenotype of T Cells Expressing Programmed Death-1 and Cytotoxic T Cell Antigen-4 in Early Lung Cancer: Local vs. Systemic Immune Response. Cancers 2019, 11, 567.

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