Tax is a potential molecular target for immunotherapy of adult T-cell leukemia/lymphoma.
We expanded CTL specific for Tax (a human T-lymphotropic virus type-1-encoded gene product) in vitro from PBMC of several adult T-cell leukemia/lymphoma (ATL) patients, and document its potential significance as a target for ATL immunotherapy. Tax-specific CTL responses against tumor cells were restricted by Tax-expression and the appropriate human leukocyte antigen (HLA) type. Tax-specific CTL recognized HLA/Tax-peptide complexes on autologous ATL cells, even when their Tax expression was so low that it could only be detected by RT-PCR but not by flow cytometry. Recognition resulted in interferon gamma (IFN-γ) production and target cell lysis. This would be the first report that Tax-specific CTL from ATL patients specifically recognized and killed autologous tumor cells that expressed Tax. The Tax-specific CTL responded to as little as 0.01 pM of the corresponding peptide, indicating that their T-cell receptor avidity was much higher than that of any other CTL recognizing viral or other tumor antigens. This is presumably the reason why the Tax-specific CTL recognized and killed autologous ATL cells despite their very low Tax expression. In addition, cell cycle analyses and experiments with primary ATL cell-bearing mice demonstrated that ATL cells present at the site of active cell proliferation, such as in the tumor masses, expressed substantial amounts of Tax, but it was minimally expressed by the tumor cells in a quiescent state, such as in the blood. The present study not only provides a strong rationale for exploiting Tax as a possible target for ATL immunotherapy but also contributes to our understanding of the immunopathogenesis of ATL.
Department of Medical Oncology & Immunology, Nagoya City University Graduate School of Medical Sciences, Japan.
Susumu
S
Suzuki
Ayako
A
Masaki
Takashi
T
Ishida
Asahi
A
Ito
Fumiko
F
Mori
Fumihiko
F
Sato
Tomoko
T
Narita
Masaki
M
Ri
Shigeru
S
Kusumoto
Hirokazu
H
Komatsu
Yasuo
Y
Fukumori
Hiroyoshi
H
Nishikawa
Yuetsu
Y
Tanaka
Akio
A
Niimi
Hiroshi
H
Inagaki
Shinsuke
S
Iida
Ryuzo
R
Ueda
D000328:Adult; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D005434:Flow Cytometry; D016356:Gene Products, tax / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000276:immunology*; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000951:Antigens, Neoplasm; D016356:Gene Products, tax