Expression of human tumor-associated antigen RCAS1 in Reed-Sternberg cellsin association with Epstein-Barr virus infection: A potential mechanism ofimmune evasion

RCASI (receptor-binding cancer antigen expressed on SiSo cells) is present in neoplastic cells, induces apoptosis of natural killer (NK)IT cells and p lays a role in immune evasion. pas ligand (FasL) is considered to have simi lar roles. The Epstein-Barr virus (EBV)-encoded latent membrane protein is expressed by malignant Hodgkin and Reed-Sternberg (H&RS) cells of EBV-assoc iated Hodgkin's disease (HD) and considered to be a target of cytotoxic T l ymphocytes (CTLs), However, CTL response is inadequate in HD. To determine whether RCASI and Fast are expressed in EBV-associated HD and participate i n immune evasion, tissues of 20 EBV- and 15 EBV+ HD cases were immunohistoc hemically stained for RCAS I, FasL and HLA classes I and II, whose deficien cies could explain CTL escape. Lymphocytes surrounding H&RS cells tended to be CD4(+) cells and rarely CD8(+), TIA-I+ (cytotoxic marker) or NK cells. HLA class I and/or II were expressed in all EBV+ HD cases, and RCASI-expres sing H&RS cells were found in 14/15 (93%) EBV+ HD cases but only 8/20 (40%) EBV- HD cases (p < 0.05), Fast was detected in 9/15 (60%) and 7/20 (35%) E BV+ and EBV HD cases, respectively. ssDNA-positive (apoptotic) lymphocytes, surrounding H&RS cells, were rarely seen but were present in RCASI cases ( 20/22 cases, 91%) rather than negative cases (0/13 cases, 0%) (p < 0.005), Our findings suggest that EBV+ H&RS cells might evade the host immune respo nse by expressing RCASI rather than Fast. (C) 2001 Wiley-Liss, Inc.