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Complementing the Cancer-Immunity Cycle

Reactivation of cytotoxic CD8(+) T-cell responses has set a new direction for cancer immunotherapy. Neutralizing antibodies targeting immune checkpoint programmed cell death protein 1 (PD-1) or its ligand (PD-L1) have been particularly successful for tumor types with limited therapeutic options such...

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Autores principales: Pio, Ruben, Ajona, Daniel, Ortiz-Espinosa, Sergio, Mantovani, Alberto, Lambris, John D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6473060/
https://www.ncbi.nlm.nih.gov/pubmed/31031765
http://dx.doi.org/10.3389/fimmu.2019.00774
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author Pio, Ruben
Ajona, Daniel
Ortiz-Espinosa, Sergio
Mantovani, Alberto
Lambris, John D.
author_facet Pio, Ruben
Ajona, Daniel
Ortiz-Espinosa, Sergio
Mantovani, Alberto
Lambris, John D.
author_sort Pio, Ruben
collection PubMed
description Reactivation of cytotoxic CD8(+) T-cell responses has set a new direction for cancer immunotherapy. Neutralizing antibodies targeting immune checkpoint programmed cell death protein 1 (PD-1) or its ligand (PD-L1) have been particularly successful for tumor types with limited therapeutic options such as melanoma and lung cancer. However, reactivation of T cells is only one step toward tumor elimination, and a substantial fraction of patients fails to respond to these therapies. In this context, combination therapies targeting more than one of the steps of the cancer-immune cycle may provide significant benefits. To find the best combinations, it is of upmost importance to understand the interplay between cancer cells and all the components of the immune response. This review focuses on the elements of the complement system that come into play in the cancer-immunity cycle. The complement system, an essential part of innate immunity, has emerged as a major regulator of cancer immunity. Complement effectors such as C1q, anaphylatoxins C3a and C5a, and their receptors C3aR and C5aR1, have been associated with tolerogenic cell death and inhibition of antitumor T-cell responses through the recruitment and/or activation of immunosuppressive cell subpopulations such as myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs), or M2 tumor-associated macrophages (TAMs). Evidence is provided to support the idea that complement blocks many of the effector routes associated with the cancer-immunity cycle, providing the rationale for new therapeutic combinations aimed to enhance the antitumor efficacy of anti-PD-1/PD-L1 checkpoint inhibitors.
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spelling pubmed-64730602019-04-26 Complementing the Cancer-Immunity Cycle Pio, Ruben Ajona, Daniel Ortiz-Espinosa, Sergio Mantovani, Alberto Lambris, John D. Front Immunol Immunology Reactivation of cytotoxic CD8(+) T-cell responses has set a new direction for cancer immunotherapy. Neutralizing antibodies targeting immune checkpoint programmed cell death protein 1 (PD-1) or its ligand (PD-L1) have been particularly successful for tumor types with limited therapeutic options such as melanoma and lung cancer. However, reactivation of T cells is only one step toward tumor elimination, and a substantial fraction of patients fails to respond to these therapies. In this context, combination therapies targeting more than one of the steps of the cancer-immune cycle may provide significant benefits. To find the best combinations, it is of upmost importance to understand the interplay between cancer cells and all the components of the immune response. This review focuses on the elements of the complement system that come into play in the cancer-immunity cycle. The complement system, an essential part of innate immunity, has emerged as a major regulator of cancer immunity. Complement effectors such as C1q, anaphylatoxins C3a and C5a, and their receptors C3aR and C5aR1, have been associated with tolerogenic cell death and inhibition of antitumor T-cell responses through the recruitment and/or activation of immunosuppressive cell subpopulations such as myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs), or M2 tumor-associated macrophages (TAMs). Evidence is provided to support the idea that complement blocks many of the effector routes associated with the cancer-immunity cycle, providing the rationale for new therapeutic combinations aimed to enhance the antitumor efficacy of anti-PD-1/PD-L1 checkpoint inhibitors. Frontiers Media S.A. 2019-04-12 /pmc/articles/PMC6473060/ /pubmed/31031765 http://dx.doi.org/10.3389/fimmu.2019.00774 Text en Copyright © 2019 Pio, Ajona, Ortiz-Espinosa, Mantovani and Lambris. 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) and the copyright owner(s) 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
Pio, Ruben
Ajona, Daniel
Ortiz-Espinosa, Sergio
Mantovani, Alberto
Lambris, John D.
Complementing the Cancer-Immunity Cycle
title Complementing the Cancer-Immunity Cycle
title_full Complementing the Cancer-Immunity Cycle
title_fullStr Complementing the Cancer-Immunity Cycle
title_full_unstemmed Complementing the Cancer-Immunity Cycle
title_short Complementing the Cancer-Immunity Cycle
title_sort complementing the cancer-immunity cycle
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6473060/
https://www.ncbi.nlm.nih.gov/pubmed/31031765
http://dx.doi.org/10.3389/fimmu.2019.00774
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