Journal Article

Aberrant expression of BCL2A1-restricted minor histocompatibility antigens in melanoma cells : application for allogeneic transplantation

MORISHIMA Yasuo, TORIKAI Hiroki, KUZUSHIMA Kiyotaka, AKATSUKA Yoshiki, YATABE Yasushi, KODERA Yoshihisa, TAKAHASHI Toshitada

2008

Overview

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 BCL2A1 and 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.

• Publisher: Springer Japan,Springer,Springer Nature B.V
• Subject: Allogeneic hematopoietic stem cell transplantation / Biological and medical sciences / Cell Line, Transformed / Dermatology / Gene Expression Regulation, Neoplastic / Graft vs Host Disease - immunology / Graft vs Host Disease - metabolism / Graft vs Tumor Effect - immunology / Hematologic and hematopoietic diseases / Hematology / Hematopoietic Stem Cell Transplantation / Humans / Immunity, Cellular / Medical sciences / Medicine / Medicine & Public Health / Melanoma / Melanoma - immunology / Melanoma - metabolism / Melanoma - therapy / Minor histocompatibility antigen / Minor Histocompatibility Antigens - biosynthesis / Minor Histocompatibility Antigens - immunology / Oligopeptides - biosynthesis / Oligopeptides - immunology / Oncology / Original Article / Proto-Oncogene Proteins c-bcl-2 - biosynthesis / Proto-Oncogene Proteins c-bcl-2 - immunology / T-Lymphocytes, Cytotoxic - immunology / T-Lymphocytes, Cytotoxic - metabolism / Transplantation, Homologous / Tumors of the skin and soft tissue. Premalignant lesions