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DNA Repair and Signaling in Immune-Related Cancer Therapy

Cancer therapy using immune checkpoint inhibitors (ICIs) is a promising clinical strategy for patients with multiple types of cancer. The expression of programmed cell death ligand-1 (PD-L1), an immune-suppressor ligand, in cancer cells is a factor that influences the efficacy of ICI therapy, partic...

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Autores principales: Kakoti, Sangeeta, Sato, Hiro, Laskar, Siddhartha, Yasuhara, Takaaki, Shibata, Atsushi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7506057/
https://www.ncbi.nlm.nih.gov/pubmed/33102516
http://dx.doi.org/10.3389/fmolb.2020.00205
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author Kakoti, Sangeeta
Sato, Hiro
Laskar, Siddhartha
Yasuhara, Takaaki
Shibata, Atsushi
author_facet Kakoti, Sangeeta
Sato, Hiro
Laskar, Siddhartha
Yasuhara, Takaaki
Shibata, Atsushi
author_sort Kakoti, Sangeeta
collection PubMed
description Cancer therapy using immune checkpoint inhibitors (ICIs) is a promising clinical strategy for patients with multiple types of cancer. The expression of programmed cell death ligand-1 (PD-L1), an immune-suppressor ligand, in cancer cells is a factor that influences the efficacy of ICI therapy, particularly in the anti-programmed cell death protein-1 (PD-1)/PD-L1 antibody therapy. PD-L1 expression in cancer cells are associated with tumor mutation burden including microsatellite instability because the accumulation of mutations in the cancer genome can produce abnormal proteins via mutant mRNAs, resulting in neoantigen production and HLA-neoantigen complex presentation in cancer cells. HLA-neoantigen presentation promotes immune activity within tumor environment; therefore, known as hot tumor. Thus, as the fidelity of DNA repair affects the generation of genomic mutations, the status of DNA repair and signaling in cancer cells can be considered prior to ICI therapy. The Cancer Genome Atlas (TCGA) and The Cancer Immunome Atlas (TCIA) database analysis showed that tumor samples harboring mutations in any non-homologous end joining, homologous recombination, or DNA damage signaling genes exhibit high neoantigen levels. Alternatively, an urgent task is to understand how the DNA damage-associated cancer treatments change the status of immune activity in patients because multiple clinical trials on combination therapy are ongoing. Recent studies demonstrated that multiple pathways regulate PD-L1 expression in cancer cells. Here, we summarize the regulation of the immune response to ICI therapy, including PD-L1 expression, and also discuss the potential strategies to improve the efficacy of ICI therapy for poor responders from the viewpoint of DNA damage response before or after DNA damage-associated cancer treatment.
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spelling pubmed-75060572020-10-22 DNA Repair and Signaling in Immune-Related Cancer Therapy Kakoti, Sangeeta Sato, Hiro Laskar, Siddhartha Yasuhara, Takaaki Shibata, Atsushi Front Mol Biosci Molecular Biosciences Cancer therapy using immune checkpoint inhibitors (ICIs) is a promising clinical strategy for patients with multiple types of cancer. The expression of programmed cell death ligand-1 (PD-L1), an immune-suppressor ligand, in cancer cells is a factor that influences the efficacy of ICI therapy, particularly in the anti-programmed cell death protein-1 (PD-1)/PD-L1 antibody therapy. PD-L1 expression in cancer cells are associated with tumor mutation burden including microsatellite instability because the accumulation of mutations in the cancer genome can produce abnormal proteins via mutant mRNAs, resulting in neoantigen production and HLA-neoantigen complex presentation in cancer cells. HLA-neoantigen presentation promotes immune activity within tumor environment; therefore, known as hot tumor. Thus, as the fidelity of DNA repair affects the generation of genomic mutations, the status of DNA repair and signaling in cancer cells can be considered prior to ICI therapy. The Cancer Genome Atlas (TCGA) and The Cancer Immunome Atlas (TCIA) database analysis showed that tumor samples harboring mutations in any non-homologous end joining, homologous recombination, or DNA damage signaling genes exhibit high neoantigen levels. Alternatively, an urgent task is to understand how the DNA damage-associated cancer treatments change the status of immune activity in patients because multiple clinical trials on combination therapy are ongoing. Recent studies demonstrated that multiple pathways regulate PD-L1 expression in cancer cells. Here, we summarize the regulation of the immune response to ICI therapy, including PD-L1 expression, and also discuss the potential strategies to improve the efficacy of ICI therapy for poor responders from the viewpoint of DNA damage response before or after DNA damage-associated cancer treatment. Frontiers Media S.A. 2020-09-08 /pmc/articles/PMC7506057/ /pubmed/33102516 http://dx.doi.org/10.3389/fmolb.2020.00205 Text en Copyright © 2020 Kakoti, Sato, Laskar, Yasuhara and Shibata. 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 Molecular Biosciences
Kakoti, Sangeeta
Sato, Hiro
Laskar, Siddhartha
Yasuhara, Takaaki
Shibata, Atsushi
DNA Repair and Signaling in Immune-Related Cancer Therapy
title DNA Repair and Signaling in Immune-Related Cancer Therapy
title_full DNA Repair and Signaling in Immune-Related Cancer Therapy
title_fullStr DNA Repair and Signaling in Immune-Related Cancer Therapy
title_full_unstemmed DNA Repair and Signaling in Immune-Related Cancer Therapy
title_short DNA Repair and Signaling in Immune-Related Cancer Therapy
title_sort dna repair and signaling in immune-related cancer therapy
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7506057/
https://www.ncbi.nlm.nih.gov/pubmed/33102516
http://dx.doi.org/10.3389/fmolb.2020.00205
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