Aberrant expression of BCL2A1-restricted minor histocompatibility antigens in melanoma cells: application for allogeneic transplantation.
It has been shown that allogeneic hematopoietic stem cell transplantation (HSCT) can be one of the therapeutic options for patients with metastatic solid tumors, such as renal cancer. However, the development of relatively severe GVHD seems to be necessary to achieve tumor regression in the current setting. Thus, it is crucial to identify minor histocompatibility antigens (mHags) only expressed in tumor cells but not GVHD target organs. In this study, we examined whether three mHags: ACC-1 and ACC-2 encoded by BCL2A1, and HA-1 encoded by HMHA1, could serve as such targets for melanoma. Real-time PCR and immunohistochemical analysis revealed that the expression of both BCL2A1and HMHA1 in melanoma cell lines and primary melanoma cells was comparable to that of hematopoietic cells. Indeed, melanoma cell lines were efficiently lysed by cytotoxic T lymphocytes specific for ACC-1, ACC-2, and HA-1. Our data suggest that targeting mHags encoded not only by HMHA1, whose aberrant expression in solid tumors has been reported, but also BCL2A1 may bring about beneficial selective graft-versus-tumor effects in a population of melanoma patients for whom these mHags are applicable.
Torikai
Hiroki
H
Division of Immunology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan.
Akatsuka
Yoshiki
Y
Division of Immunology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan. yakatsuk@aichi-cc.jp.
Yatabe
Yasushi
Y
Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Central Hospital, Nagoya, Japan.
Morishima
Yasuo
Y
Department of Hematology and Cell Therapy, Aichi Cancer Center Central Hospital, Nagoya, Japan.
Kodera
Yoshihisa
Y
Department of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan.
Kuzushima
Kiyotaka
K
Division of Immunology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan.
Takahashi
Toshitada
T
Division of Immunology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan.
D002461:Cell Line, Transformed; D015972:Gene Expression Regulation, Neoplastic; D006086:Graft vs Host Disease / Q000276:immunology / Q000378:metabolism; D020350:Graft vs Tumor Effect / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007111:Immunity, Cellular; D008545:Melanoma / Q000276:immunology / Q000378:metabolism* / Q000628:therapy*; D015778:Minor Histocompatibility Antigens / Q000096:biosynthesis* / Q000276:immunology; D009842:Oligopeptides / Q000096:biosynthesis* / Q000276:immunology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D014184:Transplantation, Homologous
C096816:BCL2-related protein A1; C110615:HA-1 antigen; D015778:Minor Histocompatibility Antigens; D009842:Oligopeptides; D019253:Proto-Oncogene Proteins c-bcl-2