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Altered CD94/NKG2A and perforin expression reduce the cytotoxic activity in malignant pleural effusions

  • Elisabetta Pace
    Correspondence
    Corresponding author: Address: Istituto di Biomedicina e Immunologia Molecolare, Consiglio Nazionale delle Ricerche, Via Ugo La Malfa, 153, 90146 Palermo, Italy. Tel.: +39 091 680 9148; fax: +39 091 680 9122.
    Affiliations
    Istituto di Biomedicina e Immunologia Molecolare, Unità di Immunopatologia e Farmacologia Clinica e Sperimentale dell’Apparato respiratorio, Consiglio Nazionale delle Ricerche, Palermo, Italy
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  • Caterina Di Sano
    Affiliations
    Istituto di Biomedicina e Immunologia Molecolare, Unità di Immunopatologia e Farmacologia Clinica e Sperimentale dell’Apparato respiratorio, Consiglio Nazionale delle Ricerche, Palermo, Italy
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  • Maria Ferraro
    Affiliations
    Istituto di Biomedicina e Immunologia Molecolare, Unità di Immunopatologia e Farmacologia Clinica e Sperimentale dell’Apparato respiratorio, Consiglio Nazionale delle Ricerche, Palermo, Italy
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  • Annalisa Tipa
    Affiliations
    Istituto di Biomedicina e Immunologia Molecolare, Unità di Immunopatologia e Farmacologia Clinica e Sperimentale dell’Apparato respiratorio, Consiglio Nazionale delle Ricerche, Palermo, Italy

    Dipartimento di Scienze Cliniche, Sezione di Malattie Respiratorie, Università di Parma, Parma, Italy
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  • Dario Olivieri
    Affiliations
    Dipartimento di Scienze Cliniche, Sezione di Malattie Respiratorie, Università di Parma, Parma, Italy
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  • Mario Spatafora
    Affiliations
    Dipartimento Biomedico di Medicina Interna e Specialistica, Sezione di Pneumologia, Università di Palermo, Palermo, Italy
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  • Roberta Santagata
    Affiliations
    Dipartimento Biomedico di Medicina Interna e Specialistica, Sezione di Pneumologia, Università di Palermo, Palermo, Italy
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  • Vincenzo Bellia
    Affiliations
    Dipartimento Biomedico di Medicina Interna e Specialistica, Sezione di Pneumologia, Università di Palermo, Palermo, Italy
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  • Mark Gjomarkaj
    Affiliations
    Istituto di Biomedicina e Immunologia Molecolare, Unità di Immunopatologia e Farmacologia Clinica e Sperimentale dell’Apparato respiratorio, Consiglio Nazionale delle Ricerche, Palermo, Italy
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Published:October 08, 2010DOI:https://doi.org/10.1016/j.ejca.2010.09.001

      Abstract

      CD94/NKG2A is an inhibitory receptor expressed by NK cells and cytotoxic lymphocytes and, upon activation by HLA-E, downregulates the cytolytic activities of these cells thus representing a tumour immune escape mechanism.
      This study was aimed at assessing whether cytotoxic lymphocytes (CD8+) and NK cells from malignant pleural effusions have a deregulated expression of CD94/NKG2A.
      The expression of membrane CD94/NKG2A and perforin was evaluated by flow-cytometry in CD8+ and NK cells from pleural effusions and autologous peripheral blood of cancer (n = 19) and congestive heart failure (CHF) (n = 11) patients. Intracellular CD94/NKG2A expression was evaluated by flow-cytometry in pleural effusion CD8+ and NK cells from cancer patients (n = 10). Cytotoxic activity against cancer cells exerted by pleural and autologous peripheral blood T lymphocytes from cancer patients was assessed by flow-cytometry assay.
      Pleural CD8+ from cancer patients showed a reduced expression of membrane CD94/NKG2A and perforin when compared to autologous peripheral blood and CHF pleural effusions. Reduced numbers of NK cells were present in pleural effusions from both cancer and CHF patients. Pleural NK from cancer patients showed a reduced expression of membrane CD94/NKG2A and perforin when compared to autologous peripheral blood. Pleural T lymphocytes from cancer patients exhibited a reduced cytotoxic activity against cancer cells when compared to autologous peripheral blood T lymphocytes. The intracellular expression of CD94/NKG2A in CD8+ and NK cells from cancer patients was higher than membrane expression.
      In conclusion, this study provides compelling evidences of new mechanisms underlying the reduced host defence against cancer within the pleural space.

      Keywords

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