Abstract
A growing body of literature links events associated with the progression and severity of immunity and inflammatory disease with the composition of the tissue extracellular matrix as defined by the matrisome. One protein in the matrisome that is common to many inflammatory diseases is the large proteoglycan versican, whose varied function is achieved through multiple isoforms and post-translational modifications of glycosaminoglycan structures. In cancer, increased levels of versican are associated with immune cell phenotype, disease prognosis and failure to respond to treatment. Whether these associations between versican expression and tumour immunity are the result of a direct role in the pathogenesis of tumours is not clear. In this review, we have focused on the role of versican in the immune response as it relates to tumour progression, with the aim of determining whether our current understanding of the immunobiology of versican warrants further study as a cancer immunotherapy target.
Highlights
In recent years, immunotherapy of cancer has achieved impressive clinical benefits [1]
Targeting versican, and in particular targeting specific structural forms of versican can maximise the therapeutic potential whilst minimizing deleterious effects that can be associated with tumour matrisome targeting
We conclude here that targeting the V0/V1 isoforms likely via the b-GAG domain, and the modifications of chondroitin sulphate (CS) may provide the most specific targeting
Summary
Immunotherapy of cancer has achieved impressive clinical benefits [1]. Targeting versican, and in particular targeting specific structural forms of versican can maximise the therapeutic potential whilst minimizing deleterious effects that can be associated with tumour matrisome targeting. We conclude here that targeting the V0/V1 isoforms likely via the b-GAG domain, and the modifications of CS may provide the most specific targeting.
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