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CTLA‐4 is constitutively expressed on tumor cells and can trigger apoptosis upon ligand interaction
Author(s) -
Contardi Elisabetta,
Palmisano Giulio L.,
Tazzari Pier Luigi,
Martelli Alberto M.,
Falà Federica,
Fabbi Marina,
Kato Tomohiro,
Lucarelli Enrico,
Donati Davide,
Polito Letizia,
Bolognesi Andrea,
Ricci Francesca,
Salvi Sandra,
Gargaglione Vittoria,
Mantero Stefano,
Alberghini Marco,
Ferrara Giovanni Battista,
Pistillo Maria Pia
Publication year - 2005
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.21155
Subject(s) - cancer research , cd86 , biology , cd80 , apoptosis , ctla 4 , cell culture , flow cytometry , cytotoxic t cell , microbiology and biotechnology , cd40 , t cell , chemistry , immunology , immune system , in vitro , biochemistry , genetics
CTLA‐4 (CD152) is a cell surface receptor that behaves as a negative regulator of the proliferation and the effector function of T cells. We have previously shown that CTLA‐4 is also expressed on neoplastic lymphoid and myeloid cells, and it can be targeted to induce apoptosis. In our study, we have extended our analysis and have discovered that surface expression of CTLA‐4 is detectable by flow cytometry on 30 of 34 (88%) cell lines derived from a variety of human malignant solid tumors including carcinoma, melanoma, neuroblastoma, rhabdomyosarcoma and osteosarcoma (but not in primary osteoblast‐like cultures). However, by reverse transcriptase‐PCR, CTLA‐4 expression was detected in all cell lines. We have also found, by immunohistochemistry, cytoplasmic and surface expression of CTLA‐4 in the tumor cells of all 6 osteosarcoma specimens examined and in the tumour cells of all 5 cases (but only weakly or no positivity at all in neighbouring nontumor cells) of ductal breast carcinomas. Treatment of cells from CTLA‐4‐expressing tumor lines with recombinant forms of the CTLA‐4‐ligands CD80 and CD86 induced apoptosis associated with sequential activation of caspase‐8 and caspase‐3. The level of apoptosis was reduced by soluble CTLA‐4 and by anti‐CTLA‐4 scFvs antibodies. The novel finding that CTLA‐4 molecule is expressed and functional on human tumor cells opens up the possibility of antitumor therapeutic intervention based on targeting this molecule. © 2005 Wiley‐Liss, Inc.