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https://hdl.handle.net/2440/72919
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Type: | Journal article |
Title: | Increased proteinase inhibitor-9 (PI-9) and reduced granzyme B in lung cancer: mechanism for immune evasion? |
Author: | Soriano, C. Mukaro, V. Hodge, G. Ahern, J. Holmes, M. Jersmann, H. Moffat, D. Meredith, D. Jurisevic, C. Reynolds, P. Hodge, S. |
Citation: | Lung Cancer, 2012; 77(1):38-45 |
Publisher: | Elsevier Sci Ireland Ltd |
Issue Date: | 2012 |
ISSN: | 0169-5002 1872-8332 |
Statement of Responsibility: | Cyd Soriano, Violet Mukaro, Greg Hodge, Jessica Ahern, Mark Holmes, Hubertus Jersmann, David Moffat, David Meredith, Craig Jurisevic, Paul N. Reynolds and Sandra Hodge |
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. |
Keywords: | Lung CD8-Positive T-Lymphocytes Cell Line, Tumor Bronchoalveolar Lavage Fluid Humans Carcinoma, Non-Small-Cell Lung Lung Neoplasms Pulmonary Disease, Chronic Obstructive Serpins Cell Extracts Culture Media, Conditioned Neoplasm Staging Case-Control Studies Cytotoxicity, Immunologic Tumor Escape Aged Middle Aged Female Male Granzymes |
Rights: | © 2012 Elsevier Ireland Ltd. All rights reserved. |
DOI: | 10.1016/j.lungcan.2012.01.017 |
Published version: | http://dx.doi.org/10.1016/j.lungcan.2012.01.017 |
Appears in Collections: | Aurora harvest Medicine publications |
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