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.
Ohshima
K
K
Department of Pathology, School of Medicine, Fukuoka University, Fukuoka, Japan. ohshima@fukuoka-u.ac.jp
Muta
K
K
Nakashima
M
M
Haraoka
S
S
Tutiya
T
T
Suzumiya
J
J
Kawasaki
C
C
Watanabe
T
T
Kikuchi
M
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm / Q000032:analysis / Q000235:genetics; D000954:Antigens, Surface / Q000032:analysis / Q000235:genetics*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002648:Child; D053222:Fas Ligand Protein; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000302:isolation & purification*; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006689:Hodgkin Disease / Q000235:genetics* / Q000276:immunology / Q000473:pathology*; D006801:Humans; D017403:In Situ Hybridization; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D016539:Reed-Sternberg Cells / Q000276:immunology / Q000473:pathology* / Q000821:virology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; C120762:EBAG9 protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D008562:Membrane Glycoproteins