MAGE-6 encodes HLA-DRβ1*0401-presented Epitopes recognized by CD4+ T cells from patients with melanoma or renal cell carcinoma

Tomohide Tatsumi, Lisa S. Kierstead, Elena Ranieri, Loreto Gesualdo, Francesco P. Schena, James H. Finke, Ronald M. Bukowski, Vladimir Brusic, John Sidney, Alessandro Sette, Theodore F. Logan, Yvette L. Kasamon, Craig L. Slingluff, John M. Kirkwood, Walter J. Storkus

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

CD4+ T cells modulate the magnitude and durability of CTL responses in vivo and may serve as potent effector cells within the tumor microenvironment. The current study was undertaken to define novel epitopes from the broadly expressed tumor antigen MAGE-6 that are recognized by CD4+ T cells. We have combined the use of a HLA-DR4/ peptide binding algorithm with the IFN-γ enzyme-linked immunospot assay to identify four nonoverlapping sequences derived from the MAGE-6 protein that served as CD4+ T-cell epitopes in HLA-DR4+ donors. Strikingly, patients with active melanoma or renal cell carcinoma failed to secrete IFN-γ in response to MAGE-6-derived epitopes, whereas both normal donors and cancer patients with no current evidence of disease were responsive, particularly after short-term in vitro stimulations with peptide-pulsed dendritic cells. Importantly, peptide-specific CD4+ T cells also recognized HLA-DRβ1*0401+ tumor cells that constitutively expressed the MAGE-6 protein and autologous HLA-DRβ1*0401+ dendritic cells transfected with MAGE-6 cDNA-elicited CD4+ T cells that reacted against individual peptide epitopes in vitro. These data suggest that MAGE-6-derived epitopes could serve as useful vaccine candidate components and may provide an immune-monitoring index of clinically important Th1-type immunity in patients with renal cell carcinoma or melanoma.

Original languageEnglish
Pages (from-to)947-954
Number of pages8
JournalClinical Cancer Research
Volume9
Issue number3
Publication statusPublished - Mar 1 2003
Externally publishedYes

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HLA-DR1 Antigen
Renal Cell Carcinoma
Epitopes
Melanoma
HLA-DR4 Antigen
T-Lymphocytes
Peptides
Dendritic Cells
Tissue Donors
Enzyme-Linked Immunospot Assay
Immunologic Monitoring
T-Lymphocyte Epitopes
Tumor Microenvironment
Neoplasm Antigens
Immunity
Neoplasms
Proteins
Vaccines
Complementary DNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Tatsumi, T., Kierstead, L. S., Ranieri, E., Gesualdo, L., Schena, F. P., Finke, J. H., ... Storkus, W. J. (2003). MAGE-6 encodes HLA-DRβ1*0401-presented Epitopes recognized by CD4+ T cells from patients with melanoma or renal cell carcinoma. Clinical Cancer Research, 9(3), 947-954.

MAGE-6 encodes HLA-DRβ1*0401-presented Epitopes recognized by CD4+ T cells from patients with melanoma or renal cell carcinoma. / Tatsumi, Tomohide; Kierstead, Lisa S.; Ranieri, Elena; Gesualdo, Loreto; Schena, Francesco P.; Finke, James H.; Bukowski, Ronald M.; Brusic, Vladimir; Sidney, John; Sette, Alessandro; Logan, Theodore F.; Kasamon, Yvette L.; Slingluff, Craig L.; Kirkwood, John M.; Storkus, Walter J.

In: Clinical Cancer Research, Vol. 9, No. 3, 01.03.2003, p. 947-954.

Research output: Contribution to journalArticle

Tatsumi, T, Kierstead, LS, Ranieri, E, Gesualdo, L, Schena, FP, Finke, JH, Bukowski, RM, Brusic, V, Sidney, J, Sette, A, Logan, TF, Kasamon, YL, Slingluff, CL, Kirkwood, JM & Storkus, WJ 2003, 'MAGE-6 encodes HLA-DRβ1*0401-presented Epitopes recognized by CD4+ T cells from patients with melanoma or renal cell carcinoma', Clinical Cancer Research, vol. 9, no. 3, pp. 947-954.
Tatsumi T, Kierstead LS, Ranieri E, Gesualdo L, Schena FP, Finke JH et al. MAGE-6 encodes HLA-DRβ1*0401-presented Epitopes recognized by CD4+ T cells from patients with melanoma or renal cell carcinoma. Clinical Cancer Research. 2003 Mar 1;9(3):947-954.
Tatsumi, Tomohide ; Kierstead, Lisa S. ; Ranieri, Elena ; Gesualdo, Loreto ; Schena, Francesco P. ; Finke, James H. ; Bukowski, Ronald M. ; Brusic, Vladimir ; Sidney, John ; Sette, Alessandro ; Logan, Theodore F. ; Kasamon, Yvette L. ; Slingluff, Craig L. ; Kirkwood, John M. ; Storkus, Walter J. / MAGE-6 encodes HLA-DRβ1*0401-presented Epitopes recognized by CD4+ T cells from patients with melanoma or renal cell carcinoma. In: Clinical Cancer Research. 2003 ; Vol. 9, No. 3. pp. 947-954.
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