Open AccessTax is a potential molecular target for immunotherapy of adult T ‐cell leukemia/lymphoma
Author(s) -
Suzuki Susumu,
Masaki Ayako,
Ishida Takashi,
Ito Asahi,
Mori Fumiko,
Sato Fumihiko,
Narita Tomoko,
Ri Masaki,
Kusumoto Shigeru,
Komatsu Hirokazu,
Fukumori Yasuo,
Nishikawa Hiroyoshi,
Tanaka Yuetsu,
Niimi Akio,
Inagaki Hiroshi,
Iida Shinsuke,
Ueda Ryuzo
Publication year - 2012
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2012.02371.x
Subject(s) - ctl* , biology , cytotoxic t cell , immunotherapy , t cell leukemia , antigen , t cell , immunology , cancer research , flow cytometry , virology , leukemia , microbiology and biotechnology , cd8 , immune system , in vitro , biochemistry
We expanded CTL specific for T ax (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 T ax‐expression and the appropriate human leukocyte antigen ( HLA ) type. Tax‐specific CTL recognized HLA/T ax‐peptide complexes on autologous ATL cells, even when their T ax 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 T ax‐specific CTL from ATL patients specifically recognized and killed autologous tumor cells that expressed T ax. The T ax‐specific CTL responded to as little as 0.01 p M 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 T ax‐specific CTL recognized and killed autologous ATL cells despite their very low T ax 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 T ax, 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 .