Peptidome from renal cell carcinoma contains antigens recognized by CD4+ T cells and shared among tumors of different histology

Elena Tassi, Valeria Facchinetti, Samantha Seresini, Anna Borri, Giacomo Dell'Antonio, Claudio Garavaglia, Giulia Casorati, Maria Pia Protti

Research output: Contribution to journalArticle

Abstract

Purpose: Renal cell carcinoma (RCC) is considered immunogenic; nonetheless, rare tumor-associated antigens have been identified or are expressed in RCC. Peptidome (i.e., the total content of natural peptides of whole cells) from other tumors, such as melanoma, has proved to be immunogenic. The aims of this study were to determine whether peptidome from RCC is immunogenic and whether it contains tumor peptides shared among allogenic RCCs. Experimental Design: Autologous dendritic cells pulsed with RCC peptidome were used to activate in vitro CD4+ T cells from healthy donors and a metastatic RCC patient. CD4+ T-cell polyclonal lines and clones were characterized for tumor cell recognition by proliferation assay, killing activity, and cytokine secretion. Results: CD4+ T-cell lines and clones recognized HLA-DR-matched allogenic RCC and, for the patient, the autologous tumor. RCC-reactive CD4+ T cells showed a heterogeneous Th1 or Th0/Th2 pattern of cytokine secretion. Moreover, RCC-reactive CD4+ T cells recognized also melanoma, colon carcinoma, cervical carcinoma, pancreas carcinoma, lung carcinoma, gastric carcinoma, and lymphoma cells but not autologous T-cell blasts. Conclusions: Our results show that (a) the RCC peptidome contain antigens recognized by CD4+ T cells and (b) shared among tumors of different histology and (c) it induces both Th1-type and Th2/Th0-type immune responses. These data support the use of the peptidome from allogenic RCC for specific immunotherapy in RCC and possibly in other neoplastic diseases. Moreover, the CD4+ T-cell clones generated here are useful tools for tumor antigen identification.

Original languageEnglish
Pages (from-to)4949-4957
Number of pages9
JournalClinical Cancer Research
Volume12
Issue number16
DOIs
Publication statusPublished - Aug 15 2006

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CD4 Antigens
Renal Cell Carcinoma
Histology
T-Lymphocytes
Neoplasms
Carcinoma
Clone Cells
Neoplasm Antigens
Melanoma
Cytokines
Cell Line
Peptides
HLA-DR Antigens
Immunotherapy
Dendritic Cells
Pancreas
Colon
Research Design
Cell Proliferation
Tissue Donors

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Peptidome from renal cell carcinoma contains antigens recognized by CD4+ T cells and shared among tumors of different histology. / Tassi, Elena; Facchinetti, Valeria; Seresini, Samantha; Borri, Anna; Dell'Antonio, Giacomo; Garavaglia, Claudio; Casorati, Giulia; Protti, Maria Pia.

In: Clinical Cancer Research, Vol. 12, No. 16, 15.08.2006, p. 4949-4957.

Research output: Contribution to journalArticle

Tassi, Elena ; Facchinetti, Valeria ; Seresini, Samantha ; Borri, Anna ; Dell'Antonio, Giacomo ; Garavaglia, Claudio ; Casorati, Giulia ; Protti, Maria Pia. / Peptidome from renal cell carcinoma contains antigens recognized by CD4+ T cells and shared among tumors of different histology. In: Clinical Cancer Research. 2006 ; Vol. 12, No. 16. pp. 4949-4957.
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T1 - Peptidome from renal cell carcinoma contains antigens recognized by CD4+ T cells and shared among tumors of different histology

AU - Tassi, Elena

AU - Facchinetti, Valeria

AU - Seresini, Samantha

AU - Borri, Anna

AU - Dell'Antonio, Giacomo

AU - Garavaglia, Claudio

AU - Casorati, Giulia

AU - Protti, Maria Pia

PY - 2006/8/15

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N2 - Purpose: Renal cell carcinoma (RCC) is considered immunogenic; nonetheless, rare tumor-associated antigens have been identified or are expressed in RCC. Peptidome (i.e., the total content of natural peptides of whole cells) from other tumors, such as melanoma, has proved to be immunogenic. The aims of this study were to determine whether peptidome from RCC is immunogenic and whether it contains tumor peptides shared among allogenic RCCs. Experimental Design: Autologous dendritic cells pulsed with RCC peptidome were used to activate in vitro CD4+ T cells from healthy donors and a metastatic RCC patient. CD4+ T-cell polyclonal lines and clones were characterized for tumor cell recognition by proliferation assay, killing activity, and cytokine secretion. Results: CD4+ T-cell lines and clones recognized HLA-DR-matched allogenic RCC and, for the patient, the autologous tumor. RCC-reactive CD4+ T cells showed a heterogeneous Th1 or Th0/Th2 pattern of cytokine secretion. Moreover, RCC-reactive CD4+ T cells recognized also melanoma, colon carcinoma, cervical carcinoma, pancreas carcinoma, lung carcinoma, gastric carcinoma, and lymphoma cells but not autologous T-cell blasts. Conclusions: Our results show that (a) the RCC peptidome contain antigens recognized by CD4+ T cells and (b) shared among tumors of different histology and (c) it induces both Th1-type and Th2/Th0-type immune responses. These data support the use of the peptidome from allogenic RCC for specific immunotherapy in RCC and possibly in other neoplastic diseases. Moreover, the CD4+ T-cell clones generated here are useful tools for tumor antigen identification.

AB - Purpose: Renal cell carcinoma (RCC) is considered immunogenic; nonetheless, rare tumor-associated antigens have been identified or are expressed in RCC. Peptidome (i.e., the total content of natural peptides of whole cells) from other tumors, such as melanoma, has proved to be immunogenic. The aims of this study were to determine whether peptidome from RCC is immunogenic and whether it contains tumor peptides shared among allogenic RCCs. Experimental Design: Autologous dendritic cells pulsed with RCC peptidome were used to activate in vitro CD4+ T cells from healthy donors and a metastatic RCC patient. CD4+ T-cell polyclonal lines and clones were characterized for tumor cell recognition by proliferation assay, killing activity, and cytokine secretion. Results: CD4+ T-cell lines and clones recognized HLA-DR-matched allogenic RCC and, for the patient, the autologous tumor. RCC-reactive CD4+ T cells showed a heterogeneous Th1 or Th0/Th2 pattern of cytokine secretion. Moreover, RCC-reactive CD4+ T cells recognized also melanoma, colon carcinoma, cervical carcinoma, pancreas carcinoma, lung carcinoma, gastric carcinoma, and lymphoma cells but not autologous T-cell blasts. Conclusions: Our results show that (a) the RCC peptidome contain antigens recognized by CD4+ T cells and (b) shared among tumors of different histology and (c) it induces both Th1-type and Th2/Th0-type immune responses. These data support the use of the peptidome from allogenic RCC for specific immunotherapy in RCC and possibly in other neoplastic diseases. Moreover, the CD4+ T-cell clones generated here are useful tools for tumor antigen identification.

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