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Strategies to reverse melanoma-induced T-cell dysfunction.

Abstract
Patients with advanced melanoma can develop spontaneous cellular and humoral responses to tumor antigens. Understanding the failure of spontaneous or vaccine-induced tumor antigen-specific T-cell responses to promote the immunologic clearance of melanomas is critical. Multiple mechanisms of melanoma-induced immune escape, which are likely to cause the failure of the spontaneous or vaccine-induced immune responses to promote tumor regression in humans, have been elucidated. In addition, a number of negative factors in the tumor microenvironment dampen antitumor immune responses, including cytokines (like transforming growth factor-β or interleukin-10), suppressive cells (regulatory T cells and myelosuppressive dendritic cells), defective antigen presentation by tumor cells (human leukocyte antigen or T antigen expression loss, antigen processing machinery defects), amino acid catabolizing enzymes (indoleamine-2-3 dioxygenase, arginase), and immune inhibitory pathways (like cytotoxic T-lymphocyte antigen 4/cluster of differentiation 28, programmed death 1/programmed death 1 ligand 1). This information has been used to develop a number of therapies to specifically target these negative regulators of antimelanoma immune responses to enhance tumor antigen-specific immune responses and to increase the likelihood of clinical benefits in patients with advanced melanoma.
AuthorsJulien Fourcade, Hassane M Zarour
JournalClinics in dermatology (Clin Dermatol) 2013 May-Jun Vol. 31 Issue 3 Pg. 251-6 ISSN: 1879-1131 [Electronic] United States
PMID23608444 (Publication Type: Journal Article)
CopyrightCopyright © 2013 Elsevier Inc. All rights reserved.
Chemical References
  • Antigens, Neoplasm
  • Cancer Vaccines
Topics
  • Antigens, Neoplasm (immunology)
  • Cancer Vaccines (immunology, therapeutic use)
  • Humans
  • Melanoma (immunology, therapy)
  • T-Lymphocytes (immunology)
  • T-Lymphocytes, Regulatory (immunology)
  • Tumor Escape (immunology)
  • Tumor Microenvironment

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