Carcinoembryonic antigen-specific but not antiviral CD4+ T cell immunity is impaired in pancreatic carcinoma patients

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Abstract

Pancreatic carcinoma is a very aggressive disease with dismal prognosis. Although evidences for tumor-specific T cell immunity exist, factors related to tumor microenvironment and the presence of immunosuppressive cytokines in patients' sera have been related to its aggressive behavior. Carcinoembryonic Ag (CEA) is overexpressed in 80-90% of pancreatic carcinomas and contains epitopes recognized by CD4+ T cells. The aim of this study was to evaluate the extent of cancerimmune surveillance and immune suppression in pancreatic carcinoma patients by comparing the anti-CEA and antiviral CD4+ T cell immunity. CD4+ T cells from 23 normal donors and 44 patients undergoing surgical resection were tested for recognition of peptides corresponding to CEA and viral naturally processed promiscuous epitopes by proliferation and cytokine release assays. Anti-CEA CD4+ T cell immunity was present in a significantly higher number of normal donors than pancreatic cancer patients. Importantly, whereas CD4+ T cells from normal donors produced mainly GM-CSF and IFN-γ, CD4+ T cells from the patients produced mainly IL-5, demonstrating a skew toward a Th2 type. On the contrary, the extent of antiviral CD4+ T cell immunity was comparable between the two groups and showed a Th1 type. The immunohistochemical analysis of tumor-infiltrating lymphocytes showed a significantly higher number of GATA-3+ compared with T-bet+ lymphoid cells, supporting a Th2 skew also at the tumor site. Collectively, these results demonstrate that Th2-immune deviation in pancreatic cancer is not generalized but tumor related and suggests that the skew might be possibly due to factor(s) present at the tumor site.

Original languageEnglish
Pages (from-to)6595-6603
Number of pages9
JournalJournal of Immunology
Volume181
Issue number9
Publication statusPublished - Nov 1 2008

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Carcinoembryonic Antigen
Antiviral Agents
Immunity
T-Lymphocytes
Tissue Donors
Pancreatic Neoplasms
Epitopes
Neoplasms
Cytokines
Tumor-Infiltrating Lymphocytes
Tumor Microenvironment
Pancreatic Carcinoma
Interleukin-5
Granulocyte-Macrophage Colony-Stimulating Factor
Immunosuppressive Agents
Lymphocytes
Peptides
Serum

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

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title = "Carcinoembryonic antigen-specific but not antiviral CD4+ T cell immunity is impaired in pancreatic carcinoma patients",
abstract = "Pancreatic carcinoma is a very aggressive disease with dismal prognosis. Although evidences for tumor-specific T cell immunity exist, factors related to tumor microenvironment and the presence of immunosuppressive cytokines in patients' sera have been related to its aggressive behavior. Carcinoembryonic Ag (CEA) is overexpressed in 80-90{\%} of pancreatic carcinomas and contains epitopes recognized by CD4+ T cells. The aim of this study was to evaluate the extent of cancerimmune surveillance and immune suppression in pancreatic carcinoma patients by comparing the anti-CEA and antiviral CD4+ T cell immunity. CD4+ T cells from 23 normal donors and 44 patients undergoing surgical resection were tested for recognition of peptides corresponding to CEA and viral naturally processed promiscuous epitopes by proliferation and cytokine release assays. Anti-CEA CD4+ T cell immunity was present in a significantly higher number of normal donors than pancreatic cancer patients. Importantly, whereas CD4+ T cells from normal donors produced mainly GM-CSF and IFN-γ, CD4+ T cells from the patients produced mainly IL-5, demonstrating a skew toward a Th2 type. On the contrary, the extent of antiviral CD4+ T cell immunity was comparable between the two groups and showed a Th1 type. The immunohistochemical analysis of tumor-infiltrating lymphocytes showed a significantly higher number of GATA-3+ compared with T-bet+ lymphoid cells, supporting a Th2 skew also at the tumor site. Collectively, these results demonstrate that Th2-immune deviation in pancreatic cancer is not generalized but tumor related and suggests that the skew might be possibly due to factor(s) present at the tumor site.",
author = "Elena Tassi and Francesca Gavazzi and Luca Albarello and Vladimir Senyukov and Renato Longhi and Paolo Dellabona and Claudio Doglioni and Marco Braga and {Di Carlo}, Valerio and Protti, {Maria Pia}",
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T1 - Carcinoembryonic antigen-specific but not antiviral CD4+ T cell immunity is impaired in pancreatic carcinoma patients

AU - Tassi, Elena

AU - Gavazzi, Francesca

AU - Albarello, Luca

AU - Senyukov, Vladimir

AU - Longhi, Renato

AU - Dellabona, Paolo

AU - Doglioni, Claudio

AU - Braga, Marco

AU - Di Carlo, Valerio

AU - Protti, Maria Pia

PY - 2008/11/1

Y1 - 2008/11/1

N2 - Pancreatic carcinoma is a very aggressive disease with dismal prognosis. Although evidences for tumor-specific T cell immunity exist, factors related to tumor microenvironment and the presence of immunosuppressive cytokines in patients' sera have been related to its aggressive behavior. Carcinoembryonic Ag (CEA) is overexpressed in 80-90% of pancreatic carcinomas and contains epitopes recognized by CD4+ T cells. The aim of this study was to evaluate the extent of cancerimmune surveillance and immune suppression in pancreatic carcinoma patients by comparing the anti-CEA and antiviral CD4+ T cell immunity. CD4+ T cells from 23 normal donors and 44 patients undergoing surgical resection were tested for recognition of peptides corresponding to CEA and viral naturally processed promiscuous epitopes by proliferation and cytokine release assays. Anti-CEA CD4+ T cell immunity was present in a significantly higher number of normal donors than pancreatic cancer patients. Importantly, whereas CD4+ T cells from normal donors produced mainly GM-CSF and IFN-γ, CD4+ T cells from the patients produced mainly IL-5, demonstrating a skew toward a Th2 type. On the contrary, the extent of antiviral CD4+ T cell immunity was comparable between the two groups and showed a Th1 type. The immunohistochemical analysis of tumor-infiltrating lymphocytes showed a significantly higher number of GATA-3+ compared with T-bet+ lymphoid cells, supporting a Th2 skew also at the tumor site. Collectively, these results demonstrate that Th2-immune deviation in pancreatic cancer is not generalized but tumor related and suggests that the skew might be possibly due to factor(s) present at the tumor site.

AB - Pancreatic carcinoma is a very aggressive disease with dismal prognosis. Although evidences for tumor-specific T cell immunity exist, factors related to tumor microenvironment and the presence of immunosuppressive cytokines in patients' sera have been related to its aggressive behavior. Carcinoembryonic Ag (CEA) is overexpressed in 80-90% of pancreatic carcinomas and contains epitopes recognized by CD4+ T cells. The aim of this study was to evaluate the extent of cancerimmune surveillance and immune suppression in pancreatic carcinoma patients by comparing the anti-CEA and antiviral CD4+ T cell immunity. CD4+ T cells from 23 normal donors and 44 patients undergoing surgical resection were tested for recognition of peptides corresponding to CEA and viral naturally processed promiscuous epitopes by proliferation and cytokine release assays. Anti-CEA CD4+ T cell immunity was present in a significantly higher number of normal donors than pancreatic cancer patients. Importantly, whereas CD4+ T cells from normal donors produced mainly GM-CSF and IFN-γ, CD4+ T cells from the patients produced mainly IL-5, demonstrating a skew toward a Th2 type. On the contrary, the extent of antiviral CD4+ T cell immunity was comparable between the two groups and showed a Th1 type. The immunohistochemical analysis of tumor-infiltrating lymphocytes showed a significantly higher number of GATA-3+ compared with T-bet+ lymphoid cells, supporting a Th2 skew also at the tumor site. Collectively, these results demonstrate that Th2-immune deviation in pancreatic cancer is not generalized but tumor related and suggests that the skew might be possibly due to factor(s) present at the tumor site.

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