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Homologous Recombination Repair Deficiency and Implications for Tumor Immunogenicity

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Department of Medical Oncology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
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Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
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Department of Medical Oncology, Rijnstate Hospital, 6815 DA Arnhem, The Netherlands
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Department of Human Genetics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
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Department of Pathology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
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Author to whom correspondence should be addressed.
Academic Editors: Dmitry V. Bulavin and Alexander Emelyanov
Cancers 2021, 13(9), 2249; https://doi.org/10.3390/cancers13092249
Received: 1 April 2021 / Revised: 29 April 2021 / Accepted: 5 May 2021 / Published: 7 May 2021
(This article belongs to the Special Issue Tumor-Promoting Functions of DNA Damage and Stress Response Signaling)
Cells possess several pathways that repair DNA damage. One of these pathways is homologous recombination repair (HR), a pathway responsible for the repair of double-strand DNA breaks. In cancer, HR is sometimes dysfunctional, leading to genomic instability. The genomic instability observed in HR-deficient (HRD) tumors has been suggested to alter immunogenicity and render these tumors more susceptible to immunotherapy. In this review, we summarize the available evidence for an association between HRD and tumor immunogenicity. Although there are indications for increased efficacy of checkpoint inhibitors in HRD tumors, data from prospective studies is needed to validate whether HRD can function as a biomarker for patient selection. The extensive overview provided here can be used to guide further research in the field.
Homologous recombination repair deficiency (HRD) can be observed in virtually all cancer types. Although HRD sensitizes tumors to DNA-damaging chemotherapy and poly(ADP-ribose) polymerase (PARP) inhibitors, all patients ultimately develop resistance to these therapies. Therefore, it is necessary to identify therapeutic regimens with a more durable efficacy. HRD tumors have been suggested to be more immunogenic and, therefore, more susceptible to treatment with checkpoint inhibitors. In this review, we describe how HRD might mechanistically affect antitumor immunity and summarize the available translational evidence for an association between HRD and antitumor immunity across multiple tumor types. In addition, we give an overview of all available clinical data on the efficacy of checkpoint inhibitors in HRD tumors and describe the evidence for using treatment strategies that combine checkpoint inhibitors with PARP inhibitors. View Full-Text
Keywords: cancer; homologous recombination repair deficiency; immune checkpoint inhibitors cancer; homologous recombination repair deficiency; immune checkpoint inhibitors
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MDPI and ACS Style

van Wilpe, S.; Tolmeijer, S.H.; Koornstra, R.H.T.; de Vries, I.J.M.; Gerritsen, W.R.; Ligtenberg, M.; Mehra, N. Homologous Recombination Repair Deficiency and Implications for Tumor Immunogenicity. Cancers 2021, 13, 2249. https://doi.org/10.3390/cancers13092249

AMA Style

van Wilpe S, Tolmeijer SH, Koornstra RHT, de Vries IJM, Gerritsen WR, Ligtenberg M, Mehra N. Homologous Recombination Repair Deficiency and Implications for Tumor Immunogenicity. Cancers. 2021; 13(9):2249. https://doi.org/10.3390/cancers13092249

Chicago/Turabian Style

van Wilpe, Sandra; Tolmeijer, Sofie H.; Koornstra, Rutger H.T.; de Vries, I. J.M.; Gerritsen, Winald R.; Ligtenberg, Marjolijn; Mehra, Niven. 2021. "Homologous Recombination Repair Deficiency and Implications for Tumor Immunogenicity" Cancers 13, no. 9: 2249. https://doi.org/10.3390/cancers13092249

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