Targeting the cutaneous lymphocyte antigen (CLA) in inflammatory and neoplastic skin conditions

ABSTRACT

Introduction: The cutaneous lymphocyte antigen interacts with E-selectin on endothelial cells and is expressed on 15% of circulating T-cells. Skin-homing T-cells express the cutaneous lymphocyte antigen and play a role in local cutaneous immunity in inflammatory reactions and neoplastic conditions.

Areas covered: Lymphocyte extravasation is the essential para-physiological mechanism enabling immune surveillance of tissues for tumors as well as effector cell recruitment to inflammatory sites.

The authors focused on skin inflammatory disorders, on cutaneous lymphoproliferative disease, and on other skin malignancies.

Expert opinion: Interfering with leukocyte extravasation has been regarded as an attractive strategy in skin disorders, in the past for inflammatory conditions and more recently for cutaneous T-cell lymphomas. Therapeutic blocking of skin-homing interactions has been attempted in psoriasis and atopic dermatitis and has been achieved in the treatment of cutaneous T-cell lymphomas. Cutaneous lymphocyte antigen is a potential molecular target for both systemic and skin-directed therapy for cutaneous T-cell lymphomas.

KEYWORDS:

• Cutaneous lymphocyte antigen
• skin homing
• t-cells
• inflammatory skin disorders
• skin cancer
• atopic dermatitis
• psoriasis
• cutaneous T-cell lymphoma

Article highlights

• Interfering with tissue-specific homing receptors in Th-mediated inflammatory diseases of the skin has been attempted but is associated with systemic toxicity.

• Mogamulizumab interferes with lymphocyte skin homing and is approved for the treatment of cutaneous T-cell lymphomas.

• An anti-CLA antibody-based therapy for cutaneous T-cell lymphomas could be highly specific and reduce the risk of serious systemic immunosuppression.

• An anti-CLA monoclonal antibody conjugated with a cytotoxic agent could be investigated as a future treatment for advanced cutaneous T-cell lymphomas.

• Photoimmunotherapy combining an anti-CLA monoclonal antibody and near-infrared irradiation may be a future innovative skin-directed therapy.

This box summarizes the key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership, or options, expert testimony, grants, or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.