A MAGE‐6‐encoded peptide is recognized by expanded lymphocytes infiltrating a spontaneously regressing human primary melanoma lesion

E Zorn, T Hercend - European journal of immunology, 1999 - Wiley Online Library
E Zorn, T Hercend
European journal of immunology, 1999Wiley Online Library
In recent years, experiments based on the in vitro stimulation of either autologous peripheral
blood lymphocytes or tumor‐infiltrating lymphocytes with melanoma cells have shown that
distinct members of the large MAGE gene family encode tumor‐associated antigenic
peptides. However, little is still known about natural anti‐MAGE responses in vivo. We have
studied a case of spontaneously regressing human melanoma, hypothesizing that in this
unique situation, the host immune system had developed an efficient cytotoxic T lymphocyte …
Abstract
In recent years, experiments based on the in vitro stimulation of either autologous peripheral blood lymphocytes or tumor‐infiltrating lymphocytes with melanoma cells have shown that distinct members of the large MAGE gene family encode tumor‐associated antigenic peptides. However, little is still known about natural anti‐MAGE responses in vivo. We have studied a case of spontaneously regressing human melanoma, hypothesizing that in this unique situation, the host immune system had developed an efficient cytotoxic T lymphocyte (CTL) response against the cancer cells. Amongst the dense tumor infiltrate, certain clonal populations of T cells were shown to be amplified, thereby suggesting that an antigen‐driven selection had occurred at the tumor site. One of the expanded tumor‐infiltrating lymphocytes was shown to be a Vβ13+ CD8+ CTL displaying a strong and selective cytotoxic activity against the autologous melanoma cells. Here we show that this cytotoxic T cell clone recognizes a MAGE‐6‐encoded peptide. MAGE‐6 is therefore the fourth gene of the MAGE family shown to encode antigenic peptide recognized by T cells. Together, these data provide further evidence that T cell responses against MAGE antigens may naturally develop in vivo.
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