6533b872fe1ef96bd12d42b1

RESEARCH PRODUCT

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

Dario OlivieriMario SpataforaRoberta SantagataAnnalisa TipaMark GjomarkajElisabetta PaceVincenzo BelliaMaria FerraroCaterina Di Sano

subject

Cancer ResearchPleural effusionLymphocyteSettore MED/10 - Malattie Dell'Apparato RespiratorioCD8-Positive T-LymphocytesInterleukin 21Pleural diseaseNeoplasmsmedicineMalignant pleural effusionCytotoxic T cellHumansAgedHeart Failurebiologybusiness.industryPerforinCancerCD8-Positive T-LymphocyteMiddle Agedmedicine.diseaseNatural Killer T-CellPleural Effusion Malignantmedicine.anatomical_structureOncologyPerforinCase-Control StudiesImmunologybiology.proteinNeoplasmNatural Killer T-CellsTumor EscapebusinessCase-Control StudieNK Cell Lectin-Like Receptor Subfamily DHumanT-Lymphocytes Cytotoxic

description

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.

yearjournalcountryeditionlanguage
2010-06-15European journal of cancer (Oxford, England : 1990)
10.1016/j.ejca.2010.09.001https://pubmed.ncbi.nlm.nih.gov/20932742