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Expression of human tumor‐associated antigen RCAS1 in Reed‐Sternberg cells in association with Epstein‐Barr virus infection: A potential mechanism of immune evasion
Author(s) -
Ohshima Koichi,
Muta Koichiro,
Nakashima Manabu,
Haraoka Seiji,
Tutiya Takeshi,
Suzumiya Junji,
Kawasaki Chika,
Watanabe Takeshi,
Kikuchi Masahiro
Publication year - 2001
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.1300
Subject(s) - cytotoxic t cell , immune system , fas ligand , ctl* , antigen , biology , immunology , cd8 , epstein–barr virus , virus , human leukocyte antigen , virology , cancer research , apoptosis , biochemistry , programmed cell death , in vitro
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. © 2001 Wiley‐Liss, Inc.