Cancer/testis antigens are novel targets of immunotherapy for adult T-cell leukemia/lymphoma.
Adult T-cell leukemia/lymphoma (ATLL) is an intractable hematologic malignancy caused by human T-lymphotropic virus type 1 (HTLV-1), which infects approximately 20 million people worldwide. Here, we have explored the possible expression of cancer/testis (CT) antigens by ATLL cells, as CT antigens are widely recognized as ideal targets of cancer immunotherapy against solid tumors. A high percentage (87.7%) of ATLL cases (n = 57) expressed CT antigens at the mRNA level: NY-ESO-1 (61.4%), MAGE-A3 (31.6%), and MAGE-A4 (61.4%). CT antigen expression was confirmed by immunohistochemistry. This contrasts with other types of lymphoma or leukemia, which scarcely express these CT antigens. Humoral immune responses, particularly against NY-ESO-1, were detected in 11.6% (5 of 43) and NY-ESO-1-specific CD8(+) T-cell responses were observed in 55.6% (5 of 9) of ATLL patients. NY-ESO-1-specific CD8(+) T cells recognized autologous ATLL cells and produced effector cytokines. Thus, ATLL cells characteristically express CT antigens and therefore vaccination with CT antigens can be an effective immunotherapy of ATLL.
Experimental Immunology, Immunology Frontier Research Center, Osaka University, Osaka, Japan.
Hiroyoshi
H
Nishikawa
Yuka
Y
Maeda
Takashi
T
Ishida
Sacha
S
Gnjatic
Eiichi
E
Sato
Fumiko
F
Mori
Daisuke
D
Sugiyama
Asahi
A
Ito
Yasuo
Y
Fukumori
Atae
A
Utsunomiya
Hiroshi
H
Inagaki
Lloyd J
LJ
Old
Ryuzo
R
Ueda
Shimon
S
Sakaguchi
D000328:Adult; D000941:Antigens / Q000276:immunology / Q000502:physiology*; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D056724:Immunity, Humoral / Q000235:genetics; D007167:Immunotherapy / Q000379:methods* / Q000639:trends; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000379:methods* / Q000639:trends; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D013737:Testis / Q000276:immunology*
D000941:Antigens; D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; C072013:MAGEA3 protein, human; C095204:MAGEA4 protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins