title: Elevated regulatory T cells, surface and intracellular CTLA-4 expression and interleukin-17 in the lung cancer microenvironment in humans.
abstract: Regulatory T cells (Tregs) play an important role in the suppression of the immune response in lung cancer. Cytotoxic T-lymphocyte antigen 4 (CTLA-4) expressed on T lymphocytes is capable of downregulating cytotoxic T cells and is constitutively expressed on Tregs. Little is known about the population of Tregs with two forms of CTLA-4: surface (s) and intracellular (in) in the lung cancer environment. Th17 cells defined by production of IL-17 have pleiotropic functions in anticancer immune response. Our aim was to detect the elements of immune response regulation in lung cancer in three compartments: by analysis of bronchoalveolar lavage fluid (BALF) from the lung affected by cancer (clBALF), healthy symmetrical lung (hlBALF) and peripheral blood (PB) from the same patient. A total of 54 samples were collected. Tregs, (s)CTLA-4, (in)CTLA-4 were detected by flow cytometry with antibodies against CD4, CD25, Foxp3, CD127, CTLA-4, and concentration of IL-17 was estimated by ELISA. We observed a significantly higher proportion of Tregs in clBALF than in hlBALF or PB (8.5 vs. 5.0 vs. 5.1%, respectively, p < 0.05). The median proportion of (in)CTLA-4+ Tregs was higher in clBALF than in hlBALF or PB (89.0, 81.5, 56.0%, p < 0.05). IL-17 concentration was the highest in clBALF-6.6 pg/ml. We observed a significant correlation between the proportion of Tregs and (in)CTLA-4+ Tregs with IL-17A concentration in clBALF. We confirmed significant differences in the proportion of regulatory elements between cancerous lung and healthy lung and PB and the usefulness of BALF analysis in evaluation of immune response regulation in local lung cancer environment.
authors.affiliation: Department of Pathomorphology, PhD Study (First Faculty of Medicine), Medical University of Warsaw, 7 Pawinskiego Street, 02-106, Warsaw, Poland.
authors.forename: Iwona
authors.initials: I
authors.lastname: Kwiecien
authors.affiliation: Department of Laboratory Diagnostics and Clinical Immunology of Developmental Age, Medical University of Warsaw, 63a Zwirki i Wigury Street, 02-091, Warsaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Stelmaszczyk-Emmel
authors.affiliation: Department of Surgery, Institute of Tuberculosis and Lung Diseases, 26 Plocka Street, 01-138, Warsaw, Poland.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Polubiec-Kownacka
authors.affiliation: Department of Surgery, Institute of Tuberculosis and Lung Diseases, 26 Plocka Street, 01-138, Warsaw, Poland.
authors.forename: Dariusz
authors.initials: D
authors.lastname: Dziedzic
authors.affiliation: Department of Internal Diseases, Pneumonology and Allergology, Medical University of Warsaw, 1a Banacha Street, 02-097, Warsaw, Poland. domagalakulawik@gmail.com.
authors.forename: Joanna
authors.initials: J
authors.lastname: Domagala-Kulawik
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D060908:CTLA-4 Antigen / Q000096:biosynthesis* / Q000276:immunology; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000276:immunology; D008175:Lung Neoplasms / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D059016:Tumor Microenvironment / Q000276:immunology*
chemical_list: D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D020381:Interleukin-17
keywords: Bronchoalveolar lavage; CTLA-4; IL-17; Lung cancer; T regulatory cells