Cargando…
Strategies to Improve the Efficacy of Dendritic Cell-Based Immunotherapy for Melanoma
Melanoma is a highly aggressive form of skin cancer that frequently metastasizes to vital organs, where it is often difficult to treat with traditional therapies such as surgery and radiation. In such cases of metastatic disease, immunotherapy has emerged in recent years as an exciting treatment opt...
Autor principal: | |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5702020/ https://www.ncbi.nlm.nih.gov/pubmed/29209327 http://dx.doi.org/10.3389/fimmu.2017.01594 |
_version_ | 1783281442259730432 |
---|---|
author | Hargadon, Kristian M. |
author_facet | Hargadon, Kristian M. |
author_sort | Hargadon, Kristian M. |
collection | PubMed |
description | Melanoma is a highly aggressive form of skin cancer that frequently metastasizes to vital organs, where it is often difficult to treat with traditional therapies such as surgery and radiation. In such cases of metastatic disease, immunotherapy has emerged in recent years as an exciting treatment option for melanoma patients. Despite unprecedented successes with immune therapy in the clinic, many patients still experience disease relapse, and others fail to respond at all, thus highlighting the need to better understand factors that influence the efficacy of antitumor immune responses. At the heart of antitumor immunity are dendritic cells (DCs), an innate population of cells that function as critical regulators of immune tolerance and activation. As such, DCs have the potential to serve as important targets and delivery agents of cancer immunotherapies. Even immunotherapies that do not directly target or employ DCs, such as checkpoint blockade therapy and adoptive cell transfer therapy, are likely to rely on DCs that shape the quality of therapy-associated antitumor immunity. Therefore, understanding factors that regulate the function of tumor-associated DCs is critical for optimizing both current and future immunotherapeutic strategies for treating melanoma. To this end, this review focuses on advances in our understanding of DC function in the context of melanoma, with particular emphasis on (1) the role of immunogenic cell death in eliciting tumor-associated DC activation, (2) immunosuppression of DC function by melanoma-associated factors in the tumor microenvironment, (3) metabolic constraints on the activation of tumor-associated DCs, and (4) the role of the microbiome in shaping the immunogenicity of DCs and the overall quality of anti-melanoma immune responses they mediate. Additionally, this review highlights novel DC-based immunotherapies for melanoma that are emerging from recent progress in each of these areas of investigation, and it discusses current issues and questions that will need to be addressed in future studies aimed at optimizing the function of melanoma-associated DCs and the antitumor immune responses they direct against this cancer. |
format | Online Article Text |
id | pubmed-5702020 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-57020202017-12-05 Strategies to Improve the Efficacy of Dendritic Cell-Based Immunotherapy for Melanoma Hargadon, Kristian M. Front Immunol Immunology Melanoma is a highly aggressive form of skin cancer that frequently metastasizes to vital organs, where it is often difficult to treat with traditional therapies such as surgery and radiation. In such cases of metastatic disease, immunotherapy has emerged in recent years as an exciting treatment option for melanoma patients. Despite unprecedented successes with immune therapy in the clinic, many patients still experience disease relapse, and others fail to respond at all, thus highlighting the need to better understand factors that influence the efficacy of antitumor immune responses. At the heart of antitumor immunity are dendritic cells (DCs), an innate population of cells that function as critical regulators of immune tolerance and activation. As such, DCs have the potential to serve as important targets and delivery agents of cancer immunotherapies. Even immunotherapies that do not directly target or employ DCs, such as checkpoint blockade therapy and adoptive cell transfer therapy, are likely to rely on DCs that shape the quality of therapy-associated antitumor immunity. Therefore, understanding factors that regulate the function of tumor-associated DCs is critical for optimizing both current and future immunotherapeutic strategies for treating melanoma. To this end, this review focuses on advances in our understanding of DC function in the context of melanoma, with particular emphasis on (1) the role of immunogenic cell death in eliciting tumor-associated DC activation, (2) immunosuppression of DC function by melanoma-associated factors in the tumor microenvironment, (3) metabolic constraints on the activation of tumor-associated DCs, and (4) the role of the microbiome in shaping the immunogenicity of DCs and the overall quality of anti-melanoma immune responses they mediate. Additionally, this review highlights novel DC-based immunotherapies for melanoma that are emerging from recent progress in each of these areas of investigation, and it discusses current issues and questions that will need to be addressed in future studies aimed at optimizing the function of melanoma-associated DCs and the antitumor immune responses they direct against this cancer. Frontiers Media S.A. 2017-11-20 /pmc/articles/PMC5702020/ /pubmed/29209327 http://dx.doi.org/10.3389/fimmu.2017.01594 Text en Copyright © 2017 Hargadon. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Hargadon, Kristian M. Strategies to Improve the Efficacy of Dendritic Cell-Based Immunotherapy for Melanoma |
title | Strategies to Improve the Efficacy of Dendritic Cell-Based Immunotherapy for Melanoma |
title_full | Strategies to Improve the Efficacy of Dendritic Cell-Based Immunotherapy for Melanoma |
title_fullStr | Strategies to Improve the Efficacy of Dendritic Cell-Based Immunotherapy for Melanoma |
title_full_unstemmed | Strategies to Improve the Efficacy of Dendritic Cell-Based Immunotherapy for Melanoma |
title_short | Strategies to Improve the Efficacy of Dendritic Cell-Based Immunotherapy for Melanoma |
title_sort | strategies to improve the efficacy of dendritic cell-based immunotherapy for melanoma |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5702020/ https://www.ncbi.nlm.nih.gov/pubmed/29209327 http://dx.doi.org/10.3389/fimmu.2017.01594 |
work_keys_str_mv | AT hargadonkristianm strategiestoimprovetheefficacyofdendriticcellbasedimmunotherapyformelanoma |