Targeting the PD-1 pathway: a promising future for the treatment of melanoma

Advanced melanoma presents a significant therapeutic challenge to clinicians. Many therapies for metastatic melanoma are limited by low response rates, severe toxicities, and/or relatively short response duration. Cancer immunotherapies that act as immune-checkpoint inhibitors to block the localized...

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Bibliographic Details
Published in:Archives of Dermatological Research 2014-08, Vol.306 (6), p.511-519
Main Authors: Mamalis, Andrew, Garcha, Manveer, Jagdeo, Jared
Format: Article
Language:English
Subjects:
Animals
Antibodies, Monoclonal - therapeutic use
Antibodies, Monoclonal, Humanized - therapeutic use
B7-H1 Antigen - immunology
Clinical Trials as Topic
Dermatology
Humans
Immunotherapy - methods
Medicine
Medicine & Public Health
Melanoma - drug therapy
Melanoma - immunology
Molecular Targeted Therapy
Neoplasm Metastasis
Programmed Cell Death 1 Receptor - immunology
Review
Signal Transduction - drug effects
Skin Neoplasms - drug therapy
Skin Neoplasms - immunology
Tumor Escape - drug effects
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Summary:Advanced melanoma presents a significant therapeutic challenge to clinicians. Many therapies for metastatic melanoma are limited by low response rates, severe toxicities, and/or relatively short response duration. Cancer immunotherapies that act as immune-checkpoint inhibitors to block the localized immune suppression mechanisms utilized by tumors are undergoing development and clinical trials. A clinically relevant immune escape mechanism in melanoma is the activation of the programmed cell death-1 (PD-1) receptor on infiltrating T cells. Activating PD-1 triggers an immune checkpoint resulting in inhibition of T cells directed against melanoma antigens and prevents the immune system from combating the melanoma. In Phase I clinical trials, two anti-PD1 therapies, Nivolumab and MK-3475, that block the PD-1 receptor to enable T cell killing have demonstrated objective tumor responses in patients with advanced melanoma. The purpose of this review is to present the available clinical evidence on anti-PD-1 and anti-PD-L1 immunotherapy for the treatment of advanced melanoma. We also discuss limitations associated with anti-PD-1 therapy. The blockade of the PD-1–PD-L1 pathway has shown promising results in clinical trials and has revolutionized melanoma immunotherapy.
ISSN:0340-3696
1432-069X
DOI:10.1007/s00403-014-1457-7