Circulating mesothelin protein and cellular antimesothelin immunity in patients with pancreatic cancer

Fabian Mc Johnston, Marcus C B Tan, Benjamin R. Tan, Matthew R. Porembka, Elizabeth M. Brunt, David C. Linehan, Peter O. Simon, Stacey Plambeck-Suess, Timothy J. Eberlein, Karl Erik Hellstrom, Ingegerd Hellstrom, William G. Hawkins, Peter Goedegebuure

Research output: Contribution to journalArticle

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Abstract

Purpose: Mesothelin is a glycoprotein expressed on normal mesothelial cells and is overexpressed in several histologic types of tumors including pancreatic adenocarcinomas. A soluble form of mesothelin has been detected in patients with ovarian cancer and malignant mesothelioma, and has prognostic value. Mesothelin has also been considered as a target for immune-based therapies. We conducted a study on the potential clinical utility of mesothelin as a biomarker for pancreatic disease and therapeutic target pancreatic cancer. Experimental Design: Tumor cell-bound and soluble mesothelin in patients was evaluated by immunohistochemistry and ELISA, respectively. The in vitro cellular immune response to mesothelin was evaluated by INFγ ELISA and intracellular cytokine staining for IFNγ in CD4+ and CD8+ T cells. The level of circulating antibodies to mesothelin was measured by ELISA. Results: All tumor tissue from patients with pancreatic adenocarcinoma expressed mesothelin (n = 10). Circulating mesothelin protein was detected in patients with pancreatic adenocarcinoma (73of 74 patients) and benign pancreatic disease (5 of 5) but not in healthy individuals. Mesothelin-specific CD4+ and CD8+ T cells were generated from peripheral blood lymphocytes of patients with pancreatic cancer in 50% of patients compared with only 20% of healthy individuals. Antibodies reactive to mesothelin were detected in <3% of either patients or healthy individuals. Conclusions: Circulating mesothelin is a useful biomarker for pancreatic disease. Furthermore, mesothelin-specific T cells can be induced in patients with pancreatic cancer. This suggests that mesothelin is a potential target for immune-based intervention strategies in pancreatic cancer.

Original languageEnglish (US)
Pages (from-to)6511-6518
Number of pages8
JournalClinical Cancer Research
Volume15
Issue number21
DOIs
StatePublished - Nov 1 2009

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Pancreatic Neoplasms
Cellular Immunity
Proteins
Pancreatic Diseases
Adenocarcinoma
Enzyme-Linked Immunosorbent Assay
mesothelin
T-Lymphocytes
Biomarkers
Neoplasms
Antibodies
Ovarian Neoplasms
Glycoproteins
Research Design
Immunohistochemistry
Lymphocytes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Johnston, F. M., Tan, M. C. B., Tan, B. R., Porembka, M. R., Brunt, E. M., Linehan, D. C., ... Goedegebuure, P. (2009). Circulating mesothelin protein and cellular antimesothelin immunity in patients with pancreatic cancer. Clinical Cancer Research, 15(21), 6511-6518. https://doi.org/10.1158/1078-0432.CCR-09-0565

Circulating mesothelin protein and cellular antimesothelin immunity in patients with pancreatic cancer. / Johnston, Fabian Mc; Tan, Marcus C B; Tan, Benjamin R.; Porembka, Matthew R.; Brunt, Elizabeth M.; Linehan, David C.; Simon, Peter O.; Plambeck-Suess, Stacey; Eberlein, Timothy J.; Hellstrom, Karl Erik; Hellstrom, Ingegerd; Hawkins, William G.; Goedegebuure, Peter.

In: Clinical Cancer Research, Vol. 15, No. 21, 01.11.2009, p. 6511-6518.

Research output: Contribution to journalArticle

Johnston, FM, Tan, MCB, Tan, BR, Porembka, MR, Brunt, EM, Linehan, DC, Simon, PO, Plambeck-Suess, S, Eberlein, TJ, Hellstrom, KE, Hellstrom, I, Hawkins, WG & Goedegebuure, P 2009, 'Circulating mesothelin protein and cellular antimesothelin immunity in patients with pancreatic cancer', Clinical Cancer Research, vol. 15, no. 21, pp. 6511-6518. https://doi.org/10.1158/1078-0432.CCR-09-0565
Johnston, Fabian Mc ; Tan, Marcus C B ; Tan, Benjamin R. ; Porembka, Matthew R. ; Brunt, Elizabeth M. ; Linehan, David C. ; Simon, Peter O. ; Plambeck-Suess, Stacey ; Eberlein, Timothy J. ; Hellstrom, Karl Erik ; Hellstrom, Ingegerd ; Hawkins, William G. ; Goedegebuure, Peter. / Circulating mesothelin protein and cellular antimesothelin immunity in patients with pancreatic cancer. In: Clinical Cancer Research. 2009 ; Vol. 15, No. 21. pp. 6511-6518.
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abstract = "Purpose: Mesothelin is a glycoprotein expressed on normal mesothelial cells and is overexpressed in several histologic types of tumors including pancreatic adenocarcinomas. A soluble form of mesothelin has been detected in patients with ovarian cancer and malignant mesothelioma, and has prognostic value. Mesothelin has also been considered as a target for immune-based therapies. We conducted a study on the potential clinical utility of mesothelin as a biomarker for pancreatic disease and therapeutic target pancreatic cancer. Experimental Design: Tumor cell-bound and soluble mesothelin in patients was evaluated by immunohistochemistry and ELISA, respectively. The in vitro cellular immune response to mesothelin was evaluated by INFγ ELISA and intracellular cytokine staining for IFNγ in CD4+ and CD8+ T cells. The level of circulating antibodies to mesothelin was measured by ELISA. Results: All tumor tissue from patients with pancreatic adenocarcinoma expressed mesothelin (n = 10). Circulating mesothelin protein was detected in patients with pancreatic adenocarcinoma (73of 74 patients) and benign pancreatic disease (5 of 5) but not in healthy individuals. Mesothelin-specific CD4+ and CD8+ T cells were generated from peripheral blood lymphocytes of patients with pancreatic cancer in 50{\%} of patients compared with only 20{\%} of healthy individuals. Antibodies reactive to mesothelin were detected in <3{\%} of either patients or healthy individuals. Conclusions: Circulating mesothelin is a useful biomarker for pancreatic disease. Furthermore, mesothelin-specific T cells can be induced in patients with pancreatic cancer. This suggests that mesothelin is a potential target for immune-based intervention strategies in pancreatic cancer.",
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AU - Brunt, Elizabeth M.

AU - Linehan, David C.

AU - Simon, Peter O.

AU - Plambeck-Suess, Stacey

AU - Eberlein, Timothy J.

AU - Hellstrom, Karl Erik

AU - Hellstrom, Ingegerd

AU - Hawkins, William G.

AU - Goedegebuure, Peter

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N2 - Purpose: Mesothelin is a glycoprotein expressed on normal mesothelial cells and is overexpressed in several histologic types of tumors including pancreatic adenocarcinomas. A soluble form of mesothelin has been detected in patients with ovarian cancer and malignant mesothelioma, and has prognostic value. Mesothelin has also been considered as a target for immune-based therapies. We conducted a study on the potential clinical utility of mesothelin as a biomarker for pancreatic disease and therapeutic target pancreatic cancer. Experimental Design: Tumor cell-bound and soluble mesothelin in patients was evaluated by immunohistochemistry and ELISA, respectively. The in vitro cellular immune response to mesothelin was evaluated by INFγ ELISA and intracellular cytokine staining for IFNγ in CD4+ and CD8+ T cells. The level of circulating antibodies to mesothelin was measured by ELISA. Results: All tumor tissue from patients with pancreatic adenocarcinoma expressed mesothelin (n = 10). Circulating mesothelin protein was detected in patients with pancreatic adenocarcinoma (73of 74 patients) and benign pancreatic disease (5 of 5) but not in healthy individuals. Mesothelin-specific CD4+ and CD8+ T cells were generated from peripheral blood lymphocytes of patients with pancreatic cancer in 50% of patients compared with only 20% of healthy individuals. Antibodies reactive to mesothelin were detected in <3% of either patients or healthy individuals. Conclusions: Circulating mesothelin is a useful biomarker for pancreatic disease. Furthermore, mesothelin-specific T cells can be induced in patients with pancreatic cancer. This suggests that mesothelin is a potential target for immune-based intervention strategies in pancreatic cancer.

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