We are not able to resolve this OAI Identifier to the repository landing page. If you are the repository manager for this record, please head to the Dashboard and adjust the settings.
Background CD6 is a lymphocyte surface co-receptor
physically associated with the T-cell receptor (TCR)/CD3
complex at the center of the immunological synapse.
There, CD6 assists in cell-to-cell contact stabilization and
modulation of activation/differentiation events through
interaction with CD166/ALCAM (activated leukocyte
cell adhesion molecule), its main reported ligand. While
accumulating evidence is attracting new interest on
targeting CD6 for therapeutic purposes in autoimmune
disorders, little is known on its potential in cancer. In an
attempt to elucidate the in vivo relevance of blocking CD6-
mediated interactions in health and disease, we explored
the consequences of expressing high circulating levels of a
soluble form CD6 (sCD6) as a decoy receptor.
Methods High sCD6 serum levels were achieved by using
transgenic C57BL/6 mice expressing human sCD6 under
the control of lymphoid-specific transcriptional elements
(shCD6LckEμTg) or wild type either transduced with
hepatotropic adeno-associated virus coding for mouse
sCD6 or undergoing repeated infusions of recombinant
human sCD6 protein. Characterization of sCD6-induced
changes was performed by ex vivo flow cytometry and
functional analyses of mouse lymphoid organ cells. The
in vivo relevance of those changes was explored by
challenging mice with subcutaneous or metastatic tumors
induced by syngeneic cancer cells of different lineage
origins.
Results Through a combination of in vitro and in vivo
studies, we show that circulating sCD6 expression
induces defective regulatory T cell (Treg) generation and
function, decreased CD166/ALCAM-mediated tumor cell
proliferation/migration and impaired galectin-induced
T-cell apoptosis, supporting the fact that sCD6 modulates
antitumor lymphocyte effector function and tumorigenesis.
Accordingly, sCD6 expression in vivo resulted in delayed
subcutaneous tumor growth and/or reduced metastasis on
challenge of mice with syngeneic cancer cells.
Conclusions Evidence is provided for the disruption
of CD6 receptor–ligand interactions as a feasible
immunomodulatory approach in cancer
Is data on this page outdated, violates copyrights or anything else? Report the problem now and we will take corresponding actions after reviewing your request.