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Single-cell immunophenotyping revealed the association of CD4+ central and CD4+ effector memory T cells linking exacerbating chronic obstructive pulmonary disease and NSCLC.
Gémes, Nikolett; Balog, József Á; Neuperger, Patrícia; Schlegl, Erzsébet; Barta, Imre; Fillinger, János; Antus, Balázs; Zvara, Ágnes; Hegedus, Zoltán; Czimmerer, Zsolt; Manczinger, Máté; Balogh, Gergo Mihály; Tóvári, József; Puskás, László G; Szebeni, Gábor J.
Afiliación
  • Gémes N; Laboratory of Functional Genomics, HUN-REN Biological Research Centre, Szeged, Hungary.
  • Balog JÁ; PhD School in Biology, University of Szeged, Szeged, Hungary.
  • Neuperger P; Laboratory of Functional Genomics, HUN-REN Biological Research Centre, Szeged, Hungary.
  • Schlegl E; Laboratory of Functional Genomics, HUN-REN Biological Research Centre, Szeged, Hungary.
  • Barta I; PhD School in Biology, University of Szeged, Szeged, Hungary.
  • Fillinger J; National Korányi Institute of Pulmonology, Budapest, Hungary.
  • Antus B; National Korányi Institute of Pulmonology, Budapest, Hungary.
  • Zvara Á; National Korányi Institute of Pulmonology, Budapest, Hungary.
  • Hegedus Z; National Korányi Institute of Pulmonology, Budapest, Hungary.
  • Czimmerer Z; Laboratory of Functional Genomics, HUN-REN Biological Research Centre, Szeged, Hungary.
  • Manczinger M; Laboratory of Bioinformatics, HUN-REN Biological Research Centre, Szeged, Hungary.
  • Balogh GM; Department of Biochemistry and Medical Chemistry, Medical School, University of Pécs, Pécs, Hungary.
  • Tóvári J; Macrophage Polarization Group, Institute of Genetics, HUN-REN Biological Research Centre, Szeged, Hungary.
  • Puskás LG; Synthetic and Systems Biology Unit, Institute of Biochemistry, HUN-REN Biological Research Centre, Szeged, Hungary.
  • Szebeni GJ; Department of Dermatology and Allergology, University of Szeged, Szeged, Hungary.
Front Immunol ; 14: 1297577, 2023.
Article en En | MEDLINE | ID: mdl-38187374
ABSTRACT

Introduction:

Tobacco smoking generates airway inflammation in chronic obstructive pulmonary disease (COPD), and its involvement in the development of lung cancer is still among the leading causes of early death. Therefore, we aimed to have a better understanding of the disbalance in immunoregulation in chronic inflammatory conditions in smoker subjects with stable COPD (stCOPD), exacerbating COPD (exCOPD), or non-small cell lung cancer (NSCLC).

Methods:

Smoker controls without chronic illness were recruited as controls. Through extensive mapping of single cells, surface receptor quantification was achieved by single-cell mass cytometry (CyTOF) with 29 antibodies. The CyTOF characterized 14 main immune subsets such as CD4+, CD8+, CD4+/CD8+, CD4-/CD8-, and γ/δ T cells and other subsets such as CD4+ or CD8+ NKT cells, NK cells, B cells, plasmablasts, monocytes, CD11cdim, mDCs, and pDCs. The CD4+ central memory (CM) T cells (CD4+/CD45RA-/CD45RO+/CD197+) and CD4+ effector memory (EM) T cells (CD4+/CD45RA-/CD45RO+/CD197-) were FACS-sorted for RNA-Seq analysis. Plasma samples were assayed by Luminex MAGPIX® for the quantitative measurement of 17 soluble immuno-oncology mediators (BTLA, CD28, CD80, CD27, CD40, CD86, CTLA-4, GITR, GITRL, HVEM, ICOS, LAG-3, PD-1, PD-L1, PD-L2, TIM-3, TLR-2) in the four studied groups.

Results:

Our focus was on T-cell-dependent differences in COPD and NSCLC, where peripheral CD4+ central memory and CD4+ effector memory cells showed a significant reduction in exCOPD and CD4+ CM showed elevation in NSCLC. The transcriptome analysis delineated a perfect correlation of differentially expressed genes between exacerbating COPD and NSCLC-derived peripheral CD4+ CM or CD4+ EM cells. The measurement of 17 immuno-oncology soluble mediators revealed a disease-associated phenotype in the peripheral blood of stCOPD, exCOPD, and NSCLC patients.

Discussion:

The applied single-cell mass cytometry, the whole transcriptome profiling of peripheral CD4+ memory cells, and the quantification of 17 plasma mediators provided complex data that may contribute to the understanding of the disbalance in immune homeostasis generated or sustained by tobacco smoking in COPD and NSCLC.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Contexto en salud: 6_ODS3_enfermedades_notrasmisibles Problema de salud: 6_chronic_obstructive_pulmonary_disease / 6_other_respiratory_diseases / 6_trachea_bronchus_lung_cancer Asunto principal: Carcinoma de Pulmón de Células no Pequeñas / Enfermedad Pulmonar Obstructiva Crónica / Neoplasias Pulmonares Tipo de estudio: Risk_factors_studies Límite: Humans Idioma: En Revista: Front Immunol Año: 2023 Tipo del documento: Article País de afiliación: Hungria

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Contexto en salud: 6_ODS3_enfermedades_notrasmisibles Problema de salud: 6_chronic_obstructive_pulmonary_disease / 6_other_respiratory_diseases / 6_trachea_bronchus_lung_cancer Asunto principal: Carcinoma de Pulmón de Células no Pequeñas / Enfermedad Pulmonar Obstructiva Crónica / Neoplasias Pulmonares Tipo de estudio: Risk_factors_studies Límite: Humans Idioma: En Revista: Front Immunol Año: 2023 Tipo del documento: Article País de afiliación: Hungria
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