TY - JOUR
T1 - A phenotype based approach for the immune monitoring of NY-ESO-1-specific CD4+ T cell responses in cancer patients
AU - Ayyoub, Maha
AU - Souleimanian, Naira E.
AU - Godefroy, Emmanuelle
AU - Scotto, Luigi
AU - Hesdorffer, Charles S.
AU - Old, Lloyd J.
AU - Valmori, Danila
N1 - Funding Information:
We would like to thank Drs. E. Hoffmann and J. Skipper (Ludwig Institute for Cancer Research) for providing the NY-ESO-1 peptides and Dr. G. Ritter (Ludwig Institute for Cancer Research) for providing the NY-ESO-1 recombinant protein. D. Valmori and M. Ayyoub are supported by the Ludwig Institute for Cancer Research and by the Cancer Research Institute.
Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2006/2
Y1 - 2006/2
N2 - Because of its frequent expression in tumors and spontaneous immunogenicity in advanced cancer patients, NY-ESO-1 is presently viewed as a prototype tumor antigen for the development of cancer vaccines. A prerequisite for the analysis of NY-ESO-1-specific T cell responses in vaccinated patients is the assessment of the complete T cell repertoire available for the antigen. Here, we have assessed frequency and fine specificity of CD4+ T cells reactive against NY-ESO-1-derived sequences in circulating lymphocytes from cancer patients with spontaneous responses to the antigen. We found that, relative to healthy donors, this frequency was only moderately increased in cancer patients. The reactivity of these cells, however, was directed against the same immunodominant regions previously identified for healthy donors. On account of these data, we developed an approach for the immune monitoring of NY-ESO-1-specific CD4+ T cell responses based on the assessment of CD4+ T cell populations of defined phenotype. Using this approach, a similar frequency of NY-ESO-1-specific CD4+ T cells was found among naive T cells of healthy donors and cancer patients. In contrast, among antigen-experienced T cells, NY-ESO-1-specific CD4+ T cells were exclusively detectable in cancer patients. We anticipate that this phenotype-based approach will be useful for the immune monitoring of vaccine-induced responses in vaccination trials using NY-ESO-1 as well as other tumor antigens.
AB - Because of its frequent expression in tumors and spontaneous immunogenicity in advanced cancer patients, NY-ESO-1 is presently viewed as a prototype tumor antigen for the development of cancer vaccines. A prerequisite for the analysis of NY-ESO-1-specific T cell responses in vaccinated patients is the assessment of the complete T cell repertoire available for the antigen. Here, we have assessed frequency and fine specificity of CD4+ T cells reactive against NY-ESO-1-derived sequences in circulating lymphocytes from cancer patients with spontaneous responses to the antigen. We found that, relative to healthy donors, this frequency was only moderately increased in cancer patients. The reactivity of these cells, however, was directed against the same immunodominant regions previously identified for healthy donors. On account of these data, we developed an approach for the immune monitoring of NY-ESO-1-specific CD4+ T cell responses based on the assessment of CD4+ T cell populations of defined phenotype. Using this approach, a similar frequency of NY-ESO-1-specific CD4+ T cells was found among naive T cells of healthy donors and cancer patients. In contrast, among antigen-experienced T cells, NY-ESO-1-specific CD4+ T cells were exclusively detectable in cancer patients. We anticipate that this phenotype-based approach will be useful for the immune monitoring of vaccine-induced responses in vaccination trials using NY-ESO-1 as well as other tumor antigens.
KW - CD4 T cells
KW - Human
KW - T cell epitopes
KW - Tumor immunity
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U2 - 10.1016/j.clim.2005.10.002
DO - 10.1016/j.clim.2005.10.002
M3 - Article
C2 - 16368270
AN - SCOPUS:32044435651
SN - 1521-6616
VL - 118
SP - 188
EP - 194
JO - Clinical Immunology
JF - Clinical Immunology
IS - 2-3
ER -