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https://hdl.handle.net/2440/72919
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dc.contributor.author | Soriano, C. | - |
dc.contributor.author | Mukaro, V. | - |
dc.contributor.author | Hodge, G. | - |
dc.contributor.author | Ahern, J. | - |
dc.contributor.author | Holmes, M. | - |
dc.contributor.author | Jersmann, H. | - |
dc.contributor.author | Moffat, D. | - |
dc.contributor.author | Meredith, D. | - |
dc.contributor.author | Jurisevic, C. | - |
dc.contributor.author | Reynolds, P. | - |
dc.contributor.author | Hodge, S. | - |
dc.date.issued | 2012 | - |
dc.identifier.citation | Lung Cancer, 2012; 77(1):38-45 | - |
dc.identifier.issn | 0169-5002 | - |
dc.identifier.issn | 1872-8332 | - |
dc.identifier.uri | http://hdl.handle.net/2440/72919 | - |
dc.description.abstract | Cytotoxic CD8(+) T-cells mount immune responses to cancer via cytotoxic pathways including granzyme B. Cancer cells are also known to develop immune evasion mechanisms. We hypothesised that lung cancer cells would over-express the granzyme B-inhibitor, proteinase inhibitor-9 (PI-9) and down-regulate granzyme B expression by neighbouring CD8(+) T-cells. We investigated PI-9 expression in lung cancer cell lines, and primary lung cancer cells obtained at curative lung resection from cancer patients with/without chronic obstructive pulmonary disease (COPD). Granzyme B and PI-9 expression was also determined in CD8(+) T-cells from the cancer and non-cancer areas of resected lung tissue and from bronchoalveolar lavage (BAL). We then evaluated the effects of conditioned media from lung cancer cell lines on granzyme B expression and the cytotoxic activity of CD8(+) T-cells. PI-9 was highly expressed in lung cancer cell lines. Increased PI-9 expression was also observed in primary cancer cells vs. epithelial cells from non-cancer tissue or bronchial brushing-derived normal primary large airway epithelial cells. Expression significantly correlated with cancer stage. Significantly reduced granzyme B was noted in CD8(+) T-cells from cancer vs. non-cancer tissue. Granzyme B production by CD8(+) T-cells was reduced in the presence of conditioned media from lung cancer cell lines. Our data suggest that lung cancer cells utilise their increased PI-9 expression to protect from granzyme B-mediated cytotoxicity as an immune evasion mechanism, a function that increases with lung cancer stage. | - |
dc.description.statementofresponsibility | Cyd Soriano, Violet Mukaro, Greg Hodge, Jessica Ahern, Mark Holmes, Hubertus Jersmann, David Moffat, David Meredith, Craig Jurisevic, Paul N. Reynolds and Sandra Hodge | - |
dc.language.iso | en | - |
dc.publisher | Elsevier Sci Ireland Ltd | - |
dc.rights | © 2012 Elsevier Ireland Ltd. All rights reserved. | - |
dc.source.uri | http://dx.doi.org/10.1016/j.lungcan.2012.01.017 | - |
dc.subject | Lung | - |
dc.subject | CD8-Positive T-Lymphocytes | - |
dc.subject | Cell Line, Tumor | - |
dc.subject | Bronchoalveolar Lavage Fluid | - |
dc.subject | Humans | - |
dc.subject | Carcinoma, Non-Small-Cell Lung | - |
dc.subject | Lung Neoplasms | - |
dc.subject | Pulmonary Disease, Chronic Obstructive | - |
dc.subject | Serpins | - |
dc.subject | Cell Extracts | - |
dc.subject | Culture Media, Conditioned | - |
dc.subject | Neoplasm Staging | - |
dc.subject | Case-Control Studies | - |
dc.subject | Cytotoxicity, Immunologic | - |
dc.subject | Tumor Escape | - |
dc.subject | Aged | - |
dc.subject | Middle Aged | - |
dc.subject | Female | - |
dc.subject | Male | - |
dc.subject | Granzymes | - |
dc.title | Increased proteinase inhibitor-9 (PI-9) and reduced granzyme B in lung cancer: mechanism for immune evasion? | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1016/j.lungcan.2012.01.017 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Jersmann, H. [0000-0003-1763-2736] | - |
dc.identifier.orcid | Reynolds, P. [0000-0002-2273-1774] | - |
dc.identifier.orcid | Hodge, S. [0000-0002-3602-9927] [0000-0002-9401-298X] | - |
Appears in Collections: | Aurora harvest Medicine publications |
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