{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T06:30:11Z","timestamp":1773297011099,"version":"3.50.1"},"reference-count":60,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2021,6,27]],"date-time":"2021-06-27T00:00:00Z","timestamp":1624752000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Immunotherapy based on two checkpoint inhibitors (ICI), programmed cell death 1 (PD-1, Nivolumab) and cytotoxic T-lymphocyte 4 (CTLA-4, Ipilimumab), has provided a significant improvement in overall survival for malignant mesothelioma (MM). Despite this major breakthrough, the median overall survival of patients treated with the two ICIs only reached 18.1 months vs. 14 months in standard chemotherapy. With an objective response rate of 40%, only a subset of patients benefits from immunotherapy. A critical step in the success of immunotherapy is the presentation of tumor-derived peptides by the major histocompatibility complex I (MHC-I) of tumor cells. These neoantigens are potentially immunogenic and trigger immune responses orchestrated by cytotoxic cells. In MM, tumor development is nevertheless characterized by a low mutation rate despite major structural chromosomal rearrangements driving oncogenesis (BAP1, NF2, CDKN2AB). In this opinion, we propose to investigate an approach based on the mechanisms of the DNA damage tolerance (DDT) pathways to increase the frequency of non-synonymous mutations. The idea is to transiently activate the error-prone DDT in order to generate neoantigens while preserving a fully competent antitumor immune response.<\/jats:p>","DOI":"10.3390\/cancers13133211","type":"journal-article","created":{"date-parts":[[2021,6,27]],"date-time":"2021-06-27T22:24:57Z","timestamp":1624832697000},"page":"3211","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Activation of DNA Damage Tolerance Pathways May Improve Immunotherapy of Mesothelioma"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5253-6451","authenticated-orcid":false,"given":"H\u00e9l\u00e8ne","family":"Brossel","sequence":"first","affiliation":[{"name":"Molecular and Cellular Epigenetics, Interdisciplinary Cluster for Applied Genoproteomics (GIGA), University of Li\u00e8ge, 4000 Liege, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5135-5982","authenticated-orcid":false,"given":"Alexis","family":"Fontaine","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Epigenetics, Interdisciplinary Cluster for Applied Genoproteomics (GIGA), University of Li\u00e8ge, 4000 Liege, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0628-7642","authenticated-orcid":false,"given":"Clotilde","family":"Hoyos","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Epigenetics, Interdisciplinary Cluster for Applied Genoproteomics (GIGA), University of Li\u00e8ge, 4000 Liege, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Majeed","family":"Jamakhani","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Epigenetics, Interdisciplinary Cluster for Applied Genoproteomics (GIGA), University of Li\u00e8ge, 4000 Liege, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0319-5600","authenticated-orcid":false,"given":"M\u00e9gane","family":"Willems","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Epigenetics, Interdisciplinary Cluster for Applied Genoproteomics (GIGA), University of Li\u00e8ge, 4000 Liege, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0459-4005","authenticated-orcid":false,"given":"Malik","family":"Hamaidia","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Epigenetics, Interdisciplinary Cluster for Applied Genoproteomics (GIGA), University of Li\u00e8ge, 4000 Liege, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0563-2213","authenticated-orcid":false,"given":"Luc","family":"Willems","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Epigenetics, Interdisciplinary Cluster for Applied Genoproteomics (GIGA), University of Li\u00e8ge, 4000 Liege, Belgium"},{"name":"Molecular Biology, Teaching and Research Centre (TERRA), Gembloux Agro-Bio Tech (GxABT), University of Li\u00e8ge, 5030 Gembloux, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"200226","DOI":"10.1183\/16000617.0226-2020","article-title":"Update on biology and management of mesothelioma","volume":"30","author":"Asciak","year":"2021","journal-title":"Eur. 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