title: High frequency of antitumor T cells in the blood of melanoma patients before and after vaccination with tumor antigens.
abstract: After vaccination of melanoma patients with MAGE antigens, we observed that even in the few patients showing tumor regression, the frequency of anti-vaccine T cells in the blood was often either undetectable or <10(-5) of CD8 T cells. This frequency being arguably too low for these cells to be sole effectors of rejection, we reexamined the contribution of T cells recognizing other tumor antigens. The presence of such antitumor T cells in melanoma patients has been widely reported. To begin assessing their contribution to vaccine-induced rejection, we evaluated their blood frequency in five vaccinated patients. The antitumor cytotoxic T lymphocyte (CTL) precursors ranged from 10(-4) to 3 x 10(-3), which is 10-10,000 times higher than the anti-vaccine CTL in the same patient. High frequencies were also observed before vaccination. In a patient showing nearly complete regression after vaccination with a MAGE-3 antigen, we observed a remarkably focused antitumoral response. A majority of CTL precursors (CTLp's) recognized antigens encoded by MAGE-C2, another cancer-germline gene. Others recognized gp100 antigens. CTLp's recognizing MAGE-C2 and gp100 antigens were already present before vaccination, but new clonotypes appeared afterwards. These results suggest that a spontaneous antitumor T cell response, which has become ineffective, can be reawakened by vaccination and contribute to tumor rejection. This notion is reinforced by the frequencies of anti-vaccine and antitumor CTLs observed inside metastases, as presented by Lurquin et al. (Lurquin, C., B. Lethe, V. Corbiere, I. Theate, N. van Baren, P.G. Coulie, and T. Boon. 2004. J. Exp. Med. 201:249-257).
authors.affiliation: Cellular Genetics Unit, Université de Louvain, B-1200 Brussels, Belgium.
authors.forename: Catherine
authors.initials: C
authors.lastname: Germeau
authors.forename: Wenbin
authors.initials: W
authors.lastname: Ma
authors.forename: Francesca
authors.initials: F
authors.lastname: Schiavetti
authors.forename: Christophe
authors.initials: C
authors.lastname: Lurquin
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Henry
authors.forename: Nathalie
authors.initials: N
authors.lastname: Vigneron
authors.forename: Francis
authors.initials: F
authors.lastname: Brasseur
authors.forename: Bernard
authors.initials: B
authors.lastname: Lethé
authors.forename: Etienne
authors.initials: E
authors.lastname: De Plaen
authors.forename: Thierry
authors.initials: T
authors.lastname: Velu
authors.forename: Thierry
authors.initials: T
authors.lastname: Boon
authors.forename: Pierre G
authors.initials: PG
authors.lastname: Coulie
mesh_terms: D000951:Antigens, Neoplasm / Q000276:immunology / Q000627:therapeutic use*; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D002452:Cell Count; D003602:Cytotoxicity, Immunologic; D006801:Humans; D008545:Melanoma / Q000097:blood* / Q000276:immunology / Q000628:therapy*; D008562:Membrane Glycoproteins / Q000276:immunology; D009363:Neoplasm Proteins / Q000276:immunology / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000473:pathology; D016896:Treatment Outcome; D058951:gp100 Melanoma Antigen
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; C072013:MAGEA3 protein, human; C405429:MAGEC2 protein, human; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C548637:PMEL protein, human; D058951:gp100 Melanoma Antigen