Ex Vivo host response to gastrointestinal cancer cells presented by autologous dendritic cells

A. Galetto, M. Contarini, A. Sapino, P. Cassoni, E. Consalvo, S. Forno, Caterina Pezzi, Vincenzo Barnaba, A. Mussa, L. Matera

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Background. Dendritic cells (DCs) capture apoptotic tumors and cross-present their antigens in the MHC class I and class II pathways for recognition by CD4+ and CD8+ T lymphocytes. Here we have tested the ability of fresh surgically resected colon and gastric cancer tumors to specifically activate host T lymphocytes when presented by autologous DCs. Methods. DCs derived from adherent blood mononuclear cells of five patients, after a 7-day culture with GM-CSF and IL-4, were exposed to apoptotic autologous tumor (AAT) or apoptotic autologous peritumor normal (AAN) cells and cultured 24 h with monocyte-conditioned medium to achieve full DC maturation. Tumor-specific response was evaluated as single-cell cytokine release in an enzyme-linked immunospot (ELISPOT) and as cytotoxicity in a cold target inhibition 51Cr-release assay. Results. AAT-DCs induced specific IFN-γ by T lymphocytes of two patients (rectal and gastric cancer), whereas in another two patients (rectal and gastric cancer) this response was depressed with a similar tumor-specific pattern and in one patient (rectal cancer) there was no response. Activation of IFN-γ release was accompanied by tumor cytotoxicity and both responses were enhanced by IL-12, indicating the functional integrity of patients' lymphocytes. Conclusion. These data show that T-cell memory against rectal/gastric carcinoma antigens can be triggered by tumor-loaded autologous DCs. However, escape mechanisms may exist among tumors of the same histological origin that can inhibit this host response. A DC-based antitumor immunological monitoring assay with autologous tumor biopsies may allow patients to be screened to determine those who are suitable candidates for immune-based immunotherapy.

Original languageEnglish
Pages (from-to)32-38
Number of pages7
JournalJournal of Surgical Research
Volume100
Issue number1
DOIs
Publication statusPublished - 2001

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Gastrointestinal Neoplasms
Dendritic Cells
Neoplasms
Rectal Neoplasms
Stomach Neoplasms
T-Lymphocytes
Antigens
Immunologic Monitoring
Interleukin-12
Granulocyte-Macrophage Colony-Stimulating Factor
Conditioned Culture Medium
Interleukin-4
Immunotherapy
Colonic Neoplasms
Monocytes
Cultured Cells
Blood Cells
Stomach
Lymphocytes
Cytokines

Keywords

  • Antitumor lymphocytes
  • Colorectal cancer
  • Cytokines
  • Cytotoxic T lymphocytes
  • Dendritic cells
  • Gastric cancer
  • Gastrointestinal cancer
  • Interferon γ
  • Tumor antigen

ASJC Scopus subject areas

  • Surgery

Cite this

Ex Vivo host response to gastrointestinal cancer cells presented by autologous dendritic cells. / Galetto, A.; Contarini, M.; Sapino, A.; Cassoni, P.; Consalvo, E.; Forno, S.; Pezzi, Caterina; Barnaba, Vincenzo; Mussa, A.; Matera, L.

In: Journal of Surgical Research, Vol. 100, No. 1, 2001, p. 32-38.

Research output: Contribution to journalArticle

Galetto, A, Contarini, M, Sapino, A, Cassoni, P, Consalvo, E, Forno, S, Pezzi, C, Barnaba, V, Mussa, A & Matera, L 2001, 'Ex Vivo host response to gastrointestinal cancer cells presented by autologous dendritic cells', Journal of Surgical Research, vol. 100, no. 1, pp. 32-38. https://doi.org/10.1006/jsre.2001.6158
Galetto, A. ; Contarini, M. ; Sapino, A. ; Cassoni, P. ; Consalvo, E. ; Forno, S. ; Pezzi, Caterina ; Barnaba, Vincenzo ; Mussa, A. ; Matera, L. / Ex Vivo host response to gastrointestinal cancer cells presented by autologous dendritic cells. In: Journal of Surgical Research. 2001 ; Vol. 100, No. 1. pp. 32-38.
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AU - Galetto, A.

AU - Contarini, M.

AU - Sapino, A.

AU - Cassoni, P.

AU - Consalvo, E.

AU - Forno, S.

AU - Pezzi, Caterina

AU - Barnaba, Vincenzo

AU - Mussa, A.

AU - Matera, L.

PY - 2001

Y1 - 2001

N2 - Background. Dendritic cells (DCs) capture apoptotic tumors and cross-present their antigens in the MHC class I and class II pathways for recognition by CD4+ and CD8+ T lymphocytes. Here we have tested the ability of fresh surgically resected colon and gastric cancer tumors to specifically activate host T lymphocytes when presented by autologous DCs. Methods. DCs derived from adherent blood mononuclear cells of five patients, after a 7-day culture with GM-CSF and IL-4, were exposed to apoptotic autologous tumor (AAT) or apoptotic autologous peritumor normal (AAN) cells and cultured 24 h with monocyte-conditioned medium to achieve full DC maturation. Tumor-specific response was evaluated as single-cell cytokine release in an enzyme-linked immunospot (ELISPOT) and as cytotoxicity in a cold target inhibition 51Cr-release assay. Results. AAT-DCs induced specific IFN-γ by T lymphocytes of two patients (rectal and gastric cancer), whereas in another two patients (rectal and gastric cancer) this response was depressed with a similar tumor-specific pattern and in one patient (rectal cancer) there was no response. Activation of IFN-γ release was accompanied by tumor cytotoxicity and both responses were enhanced by IL-12, indicating the functional integrity of patients' lymphocytes. Conclusion. These data show that T-cell memory against rectal/gastric carcinoma antigens can be triggered by tumor-loaded autologous DCs. However, escape mechanisms may exist among tumors of the same histological origin that can inhibit this host response. A DC-based antitumor immunological monitoring assay with autologous tumor biopsies may allow patients to be screened to determine those who are suitable candidates for immune-based immunotherapy.

AB - Background. Dendritic cells (DCs) capture apoptotic tumors and cross-present their antigens in the MHC class I and class II pathways for recognition by CD4+ and CD8+ T lymphocytes. Here we have tested the ability of fresh surgically resected colon and gastric cancer tumors to specifically activate host T lymphocytes when presented by autologous DCs. Methods. DCs derived from adherent blood mononuclear cells of five patients, after a 7-day culture with GM-CSF and IL-4, were exposed to apoptotic autologous tumor (AAT) or apoptotic autologous peritumor normal (AAN) cells and cultured 24 h with monocyte-conditioned medium to achieve full DC maturation. Tumor-specific response was evaluated as single-cell cytokine release in an enzyme-linked immunospot (ELISPOT) and as cytotoxicity in a cold target inhibition 51Cr-release assay. Results. AAT-DCs induced specific IFN-γ by T lymphocytes of two patients (rectal and gastric cancer), whereas in another two patients (rectal and gastric cancer) this response was depressed with a similar tumor-specific pattern and in one patient (rectal cancer) there was no response. Activation of IFN-γ release was accompanied by tumor cytotoxicity and both responses were enhanced by IL-12, indicating the functional integrity of patients' lymphocytes. Conclusion. These data show that T-cell memory against rectal/gastric carcinoma antigens can be triggered by tumor-loaded autologous DCs. However, escape mechanisms may exist among tumors of the same histological origin that can inhibit this host response. A DC-based antitumor immunological monitoring assay with autologous tumor biopsies may allow patients to be screened to determine those who are suitable candidates for immune-based immunotherapy.

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KW - Cytotoxic T lymphocytes

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KW - Interferon γ

KW - Tumor antigen

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