Expression of human tumor-associated antigen RCAS1 in Reed-Sternberg cells in association with Epstein-Barr virus infection: a potential mechanism of immune evasion

RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) is present in neoplastic cells, induces apoptosis of natural killer (NK)/T cells and plays a role in immune evasion. Fas ligand (FasL) is considered to have similar roles. The Epstein-Barr virus (EBV)-encoded latent membrane protein is expressed by malignant Hodgkin and Reed-Sternberg (H&RS) cells of EBV-associated Hodgkin's disease (HD) and considered to be a target of cytotoxic T lymphocytes (CTLs). However, CTL response is inadequate in HD. To determine whether RCAS1 and FasL are expressed in EBV-associated HD and participate in immune evasion, tissues of 20 EBV(-) and 15 EBV(+) HD cases were immunohistochemically stained for RCAS1, FasL and HLA classes I and II, whose deficiencies could explain CTL escape. Lymphocytes surrounding H&RS cells tended to be CD4(+) cells and rarely CD8(+), TIA-1(+) (cytotoxic marker) or NK cells. HLA class I and/or II were expressed in all EBV(+) HD cases, and RCAS1-expressing H&RS cells were found in 14/15 (93%) EBV(+) HD cases but only 8/20 (40%) EBV(-) HD cases (p < 0.05). FasL was detected in 9/15 (60%) and 7/20 (35%) EBV(+) and EBV(-) HD cases, respectively. ssDNA-positive (apoptotic) lymphocytes, surrounding H&RS cells, were rarely seen but were present in RCAS1(+) 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 response by expressing RCAS1 rather than FasL.