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Arch Dermatol Res. 2014 Aug;306(6):511-9. doi: 10.1007/s00403-014-1457-7. Epub 2014 Mar 11.

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

Author information

1
Department of Dermatology, University of California at Davis, 3301 C Street, Sacramento, CA, 95816, USA, andrewmamalis@gmail.com.

Abstract

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.

PMID:
24615548
PMCID:
PMC4110159
DOI:
10.1007/s00403-014-1457-7
[Indexed for MEDLINE]
Free PMC Article

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