Archives of Dermatological Research

, Volume 306, Issue 6, pp 511–519

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

Review

DOI: 10.1007/s00403-014-1457-7

Cite this article as:
Mamalis, A., Garcha, M. & Jagdeo, J. Arch Dermatol Res (2014) 306: 511. doi:10.1007/s00403-014-1457-7

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.

Keywords

NivolumabMK-3475IpilimumabPD-1PD-L1Programmed cell death receptor 1ImmunotherapyMelanomaBRAF

Abbreviations

ASCO

American Society of Clinical Oncology conference

CRC

Colorectal cancer

CTLA-4

Cytotoxic T-lymphocyte antigen-4

mAb

Monoclonal antibody

PD-1

Programmed cell death-1 receptor

PD-L1

Programmed cell death-1 receptor ligand

RCC

Renal cell carcinoma

RECIST

Response evaluation criteria in solid tumors

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Andrew Mamalis
    • 1
    • 2
  • Manveer Garcha
    • 1
    • 2
  • Jared Jagdeo
    • 1
    • 2
    • 3
  1. 1.Department of DermatologyUniversity of California at DavisSacramentoUSA
  2. 2.Dermatology ServiceSacramento VA Medical CenterMatherUSA
  3. 3.Department of DermatologySUNY Downstate Medical CenterBrooklynUSA