TY - JOUR
T1 - Polyfunctionality of a DKK1 self-antigen-specific CD8+ T lymphocyte clone in lung cancer
AU - Forget, Marie Andrée
AU - Reuben, Alexandre
AU - Turcotte, Simon
AU - Martin, Jocelyne
AU - Lapointe, Réjean
N1 - Funding Information:
Acknowledgments Clinical samples from breast cancer patients were provided by the Breast Cancer Bank from CHUM, a component of the FRSQ Cancer Network, and we kindly thank Urszula Krzemien for the management of clinical samples and databases. Réjean Lapointe and Marie-Andrée Forget were supported by fellowships from Fonds de la recherche en santé du Québec (FRSQ), and MAF was also funded by a Canderel fellowship from the Institut du Cancer de Montréal. This work was supported by the Canadian Institutes of Health Research (MOP-62709).
PY - 2011/8
Y1 - 2011/8
N2 - Polyfunctionality is the capacity of a T-cell to execute a variety of effector functions mainly mediated by production of cytokines, chemokines, and cytolytic enzymes. Studies in anti-viral immunity have acknowledged the importance of polyfunctionality in the clearance of infections and maintenance of protection. Although accepted in the field, this concept has not been as well characterized in cancer immunology. Here, we report the polyfunctionality profile analysis of a CD8+ T-cell clone isolated from a lung cancer patient and directed against Dickkopf-1, a potentially new tumor-associated antigen (TAA). The clone showed Tc1/Th1 effector tendencies confirmed by secretion of cytokines such as IFN-γ, IP-10, MIP-1β, MIP-1α, IL-2, GM-CSF, and expression of cytolytic enzyme granzyme B. This secretion profile is of particular interest in the context of an anti-tumor response. Although secretion of IL-5 and IL-13 was also detected, absence of IL-4 and IL-10 opposes the idea of cytokine-dependent Th1 inhibition. Establishing a comprehensive cytokine secretion profile may help predict T cells' specific response against a novel TAA in a peptide vaccination context. It may further help in selecting clones with an optimal functional profile from the peripheral blood of cancer patients for expansion and adoptive cell transfer therapy.
AB - Polyfunctionality is the capacity of a T-cell to execute a variety of effector functions mainly mediated by production of cytokines, chemokines, and cytolytic enzymes. Studies in anti-viral immunity have acknowledged the importance of polyfunctionality in the clearance of infections and maintenance of protection. Although accepted in the field, this concept has not been as well characterized in cancer immunology. Here, we report the polyfunctionality profile analysis of a CD8+ T-cell clone isolated from a lung cancer patient and directed against Dickkopf-1, a potentially new tumor-associated antigen (TAA). The clone showed Tc1/Th1 effector tendencies confirmed by secretion of cytokines such as IFN-γ, IP-10, MIP-1β, MIP-1α, IL-2, GM-CSF, and expression of cytolytic enzyme granzyme B. This secretion profile is of particular interest in the context of an anti-tumor response. Although secretion of IL-5 and IL-13 was also detected, absence of IL-4 and IL-10 opposes the idea of cytokine-dependent Th1 inhibition. Establishing a comprehensive cytokine secretion profile may help predict T cells' specific response against a novel TAA in a peptide vaccination context. It may further help in selecting clones with an optimal functional profile from the peripheral blood of cancer patients for expansion and adoptive cell transfer therapy.
KW - Dickkopf-1 (DKK1)
KW - Lung cancer
KW - Polyfunctionality
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U2 - 10.1007/s00262-011-1055-x
DO - 10.1007/s00262-011-1055-x
M3 - Article
C2 - 21681374
AN - SCOPUS:79960911859
SN - 0340-7004
VL - 60
SP - 1119
EP - 1125
JO - Cancer Immunology, Immunotherapy
JF - Cancer Immunology, Immunotherapy
IS - 8
ER -