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High frequency of antitumor T cells in the blood of melanoma patients before and after vaccination with tumor antigens

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Germeau, Catherine [UCL] Ma, Wenbin [UCL] Schiavetti, Francesca [UCL] Lurquin, Christophe [UCL] Henry, Emmanuelle [UCL] Vigneron, Nathalie [UCL] Brasseur, Francis [UCL] LETHE, Bernard [UCL] De Plaen, Etienne [UCL] Boon, Thierry [UCL] Coulie, Pierre G. [UCL]

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).

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès libre
Publication date 2005
Language Anglais
Journal information "The Journal of Experimental Medicine" - Vol. 201, no. 2, p. 241-248 (2005)
Peer reviewed yes
Publisher Rockefeller Univ Press (New York)
issn 0022-1007
e-issn 1540-9538
Publication status Publié
Affiliations UCL - MD/MIGE - Département de microbiologie, d'immunologie et de génétique
UCL - MD/MINT - Département de médecine interne
UCL - (SLuc) Unité d'oncologie médicale
UCL - MD/BICL - Département de biochimie et de biologie cellulaire
MESH Subject gp100 Melanoma Antigen ; Treatment Outcome ; T-Lymphocytes, Cytotoxic - immunology - pathology ; T-Lymphocytes - immunology ; Neoplasm Proteins - immunology - therapeutic use ; Membrane Glycoproteins - immunology ; Melanoma - blood - immunology - therapy ; Humans ; Cytotoxicity, Immunologic ; Cell Count ; Cancer Vaccines - immunology - therapeutic use ; Antigens, Neoplasm - immunology - therapeutic use
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Bibliographic reference Germeau, Catherine ; Ma, Wenbin ; Schiavetti, Francesca ; Lurquin, Christophe ; Henry, Emmanuelle ; et. al. High frequency of antitumor T cells in the blood of melanoma patients before and after vaccination with tumor antigens. In: The Journal of Experimental Medicine, Vol. 201, no. 2, p. 241-248 (2005)
Permanent URL http://hdl.handle.net/2078.1/39589