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CD40‐CD40 ligand (CD154) engagement is required but not sufficient for modulating MHC class I, ICAM‐1 and Fas expression and proliferation of human non‐small cell lung tumors
Author(s) -
Yamada Makoto,
Shiroko Takashi,
Kawaguchi Yoshihiro,
Sugiyama Yasuyuki,
Egilmez Nejat K.,
Chen FangAn,
Bankert Richard B.
Publication year - 2001
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.1224
Subject(s) - cd40 , cd154 , biology , cancer research , major histocompatibility complex , mhc class ii , cell , pathology , microbiology and biotechnology , immunology , immune system , cytotoxic t cell , medicine , in vitro , genetics
To determine the possible functional significance of CD40 expression on human non‐small cell lung carcinomas and to assess the potential of CD40 as a therapeutic target, 18 lung tumor cell lines were established from biopsy tissues and were monitored for phenotypic changes on the cell surface and alterations in tumor cell proliferation after the ligation of CD40 with a trimeric fusion protein complex of CD40 ligand (CD40Lt). CD40 cross‐linking resulted in up to a 6‐fold increase in the surface expression of major histocompatibility complex (MHC) class I, Fas and intracellular adhesion molecule (ICAM)‐1 in a subset of tumors expressing the highest levels of CD40. Suppression of tumor proliferation was seen after the ligation of CD40 on CD40Lt‐responsive cell lines. The suppression was dose dependent, reversible and resulted from a delay of the tumor cells entering S‐phase. No change in the cell phenotype or in proliferation were observed in CD40‐negative tumors or in tumors expressing moderate‐to‐low levels of CD40 after incubation with CD40Lt. CD40‐negative tumors transfected with the CD40 gene expressed high levels of CD40 on their surface, but were also unresponsive to CD40Lt cross‐linking of CD40. Our data establish that CD40 is required (but not sufficient) for transducing a signal that results in phenotypic changes in human lung tumors and suppression in their proliferation. We conclude that CD40 on non‐small cell lung tumors may represent a potential therapeutic target, but only on a subset of the CD40+ tumors. © 2001 Wiley‐Liss, Inc.