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MAGE-6 encodes HLA-DRbeta1*0401-presented epitopes recognized by CD4+ T cells from patients with melanoma or renal cell carcinoma.
Clin Cancer Res 2003; 9(3):947-54CC

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-gamma 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-gamma 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-DRbeta1*0401+ tumor cells that constitutively expressed the MAGE-6 protein and autologous HLA-DRbeta1*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.

Authors+Show Affiliations

Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12631591

Citation

Tatsumi, Tomohide, et al. "MAGE-6 Encodes HLA-DRbeta1*0401-presented Epitopes Recognized By CD4+ T Cells From Patients With Melanoma or Renal Cell Carcinoma." Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, vol. 9, no. 3, 2003, pp. 947-54.
Tatsumi T, Kierstead LS, Ranieri E, et al. MAGE-6 encodes HLA-DRbeta1*0401-presented epitopes recognized by CD4+ T cells from patients with melanoma or renal cell carcinoma. Clin Cancer Res. 2003;9(3):947-54.
Tatsumi, T., Kierstead, L. S., Ranieri, E., Gesualdo, L., Schena, F. P., Finke, J. H., ... Storkus, W. J. (2003). MAGE-6 encodes HLA-DRbeta1*0401-presented epitopes recognized by CD4+ T cells from patients with melanoma or renal cell carcinoma. Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 9(3), pp. 947-54.
Tatsumi T, et al. MAGE-6 Encodes HLA-DRbeta1*0401-presented Epitopes Recognized By CD4+ T Cells From Patients With Melanoma or Renal Cell Carcinoma. Clin Cancer Res. 2003;9(3):947-54. PubMed PMID: 12631591.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MAGE-6 encodes HLA-DRbeta1*0401-presented epitopes recognized by CD4+ T cells from patients with melanoma or renal cell carcinoma. AU - Tatsumi,Tomohide, AU - Kierstead,Lisa S, AU - Ranieri,Elena, AU - Gesualdo,Loreto, AU - Schena,Francesco P, AU - Finke,James H, AU - Bukowski,Ronald M, AU - Brusic,Vladimir, AU - Sidney,John, AU - Sette,Alessandro, AU - Logan,Theodore F, AU - Kasamon,Yvette L, AU - Slingluff,Craig L,Jr AU - Kirkwood,John M, AU - Storkus,Walter J, PY - 2003/3/13/pubmed PY - 2003/10/4/medline PY - 2003/3/13/entrez SP - 947 EP - 54 JF - Clinical cancer research : an official journal of the American Association for Cancer Research JO - Clin. Cancer Res. VL - 9 IS - 3 N2 - 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-gamma 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-gamma 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-DRbeta1*0401+ tumor cells that constitutively expressed the MAGE-6 protein and autologous HLA-DRbeta1*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. SN - 1078-0432 UR - https://www.unboundmedicine.com/medline/citation/12631591/MAGE_6_encodes_HLA_DRbeta1_0401_presented_epitopes_recognized_by_CD4+_T_cells_from_patients_with_melanoma_or_renal_cell_carcinoma_ L2 - http://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=12631591 DB - PRIME DP - Unbound Medicine ER -