{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T12:31:24Z","timestamp":1793881884704,"version":"4.7.0"},"reference-count":88,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2021,6,28]],"date-time":"2021-06-28T00:00:00Z","timestamp":1624838400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["MFAG24534"],"award-info":[{"award-number":["MFAG24534"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["IG24365"],"award-info":[{"award-number":["IG24365"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Multiple myeloma (MM) is the second most common hematologic malignancy, characterized by a multi-step evolutionary path, which starts with an early asymptomatic stage, defined as monoclonal gammopathy of undetermined significance (MGUS) evolving to overt disease in 1% of cases per year, often through an intermediate phase known as \u201csmoldering\u201d MM (sMM). Interestingly, while many genomic alterations (translocation, deletions, mutations) are usually found at early stages, they are not sufficient (alone) to determine disease evolution. The latter, indeed, relies on significant \u201cepigenetic\u201d alterations of different normal cell populations within the bone marrow (BM) niche, including the \u201cevasion\u201d from immune-system control. Additionally, MM cells could \u201ceducate\u201d the BM immune microenvironment (BM-IM) towards a pro-inflammatory and immunosuppressive phenotype, which ultimately leads to disease evolution, drug resistance, and patients\u2019 worse outcome. Indeed, it is not a case that the most important drugs for the treatment of MM include immunomodulatory agents (thalidomide, lenalidomide, and pomalidomide) and monoclonal antibodies (daratumumab, isatuximab, and elotuzumab). On these bases, in this review, we describe the most recent advances in the comprehension of the role of the different cells composing the BM-IM, and we discuss the potential molecular targets, which could represent new opportunities to improve current treatment strategies for MM patients.<\/jats:p>","DOI":"10.3390\/cancers13133213","type":"journal-article","created":{"date-parts":[[2021,6,28]],"date-time":"2021-06-28T02:05:37Z","timestamp":1624845937000},"page":"3213","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Mechanisms of Immune Evasion in Multiple Myeloma: Open Questions and Therapeutic Opportunities"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1522-4504","authenticated-orcid":false,"given":"Cirino","family":"Botta","sequence":"first","affiliation":[{"name":"Hematology Unit, Annunziata Hospital of Cosenza, 87100 Cosenza, Italy"},{"name":"Unit of Hematology, Department of Health Promotion, Maternal-Infant, Internal and Specialized Medicine of Excellence G. D\u2019Alessandro, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6339-632X","authenticated-orcid":false,"given":"Francesco","family":"Mendicino","sequence":"additional","affiliation":[{"name":"Hematology Unit, Annunziata Hospital of Cosenza, 87100 Cosenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrica Antonia","family":"Martino","sequence":"additional","affiliation":[{"name":"Hematology Unit, Annunziata Hospital of Cosenza, 87100 Cosenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernesto","family":"Vigna","sequence":"additional","affiliation":[{"name":"Hematology Unit, Annunziata Hospital of Cosenza, 87100 Cosenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4824-3445","authenticated-orcid":false,"given":"Domenica","family":"Ronchetti","sequence":"additional","affiliation":[{"name":"Department of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierpaolo","family":"Correale","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit, Grand Metropolitan Hospital \u201cBianchi-Melacrino-Morelli\u201d, 89124 Reggio Calabria, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fortunato","family":"Morabito","sequence":"additional","affiliation":[{"name":"Hematology and Bone Marrow Transplant Unit, Hemato-Oncology Department, Augusta Victoria Hospital, East Jerusalem 91191, Israel"},{"name":"Biothecnology Research Unit, AO of Cosenza, 87100 Cosenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonino","family":"Neri","sequence":"additional","affiliation":[{"name":"Department of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, Italy"},{"name":"Hematology, Fondazione IRCCS C\u00e0 Granda, Ospedale Maggiore Policlinico, 20122 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5256-0726","authenticated-orcid":false,"given":"Massimo","family":"Gentile","sequence":"additional","affiliation":[{"name":"Hematology Unit, Annunziata Hospital of Cosenza, 87100 Cosenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1007\/s00262-015-1711-7","article-title":"Phase I trial of thymidylate synthase poly-epitope peptide (TSPP) vaccine in advanced cancer patients","volume":"64","author":"Cusi","year":"2015","journal-title":"Cancer Immunol. 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