title: Polyfunctionality of a DKK1 self-antigen-specific CD8(+) T lymphocyte clone in lung cancer.
abstract: 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.
authors.affiliation: Department of Medicine, Centre de recherche, Centre hospitalier de l'Université de Montréal, Hôpital Notre-Dame, Université de Montréal, and Institut du Cancer de Montréal, Pavillon JA DeSève, Room Y-5605, 2099 rue Alexandre DeSève, Montréal, QC, Canada.
authors.forename: Marie-Andrée
authors.initials: MA
authors.lastname: Forget
authors.forename: Alexandre
authors.initials: A
authors.lastname: Reuben
authors.forename: Simon
authors.initials: S
authors.lastname: Turcotte
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Martin
authors.forename: Réjean
authors.initials: R
authors.lastname: Lapointe
mesh_terms: D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism; D001324:Autoantigens / Q000276:immunology / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002999:Clone Cells; D019295:Computational Biology; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000378:metabolism; D053804:Granzymes / Q000378:metabolism; D015234:HLA-A Antigens / Q000378:metabolism; D015789:HLA-A2 Antigen; D006801:Humans; D016219:Immunotherapy, Adoptive; D036341:Intercellular Signaling Peptides and Proteins / Q000276:immunology / Q000378:metabolism*; D008175:Lung Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D018417:Th1 Cells / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D001324:Autoantigens; D016207:Cytokines; C501126:DKK1 protein, human; D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D036341:Intercellular Signaling Peptides and Proteins; D010446:Peptide Fragments; D053804:Granzymes