{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:02:19Z","timestamp":1791234139438,"version":"4.1.0"},"reference-count":33,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T00:00:00Z","timestamp":1736899200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Education, University and Research (MIUR)","award":["PRIN 2022 PNRR"],"award-info":[{"award-number":["PRIN 2022 PNRR"]}]},{"name":"Italian Ministry of Education, University and Research (MIUR)","award":["PRIN 2017"],"award-info":[{"award-number":["PRIN 2017"]}]},{"name":"Italian Ministry of Education, University and Research (MIUR)","award":["PRIN 2022"],"award-info":[{"award-number":["PRIN 2022"]}]},{"name":"Italian Ministry of Education, University and Research (MIUR)","award":["PNRR-MCNT2-2023-12378122"],"award-info":[{"award-number":["PNRR-MCNT2-2023-12378122"]}]},{"name":"Italian Ministry of Education, University and Research (MIUR)","award":["PNRR-MAD-2022-12375909"],"award-info":[{"award-number":["PNRR-MAD-2022-12375909"]}]},{"name":"Italian Ministry of Health","award":["PRIN 2022 PNRR"],"award-info":[{"award-number":["PRIN 2022 PNRR"]}]},{"name":"Italian Ministry of Health","award":["PRIN 2017"],"award-info":[{"award-number":["PRIN 2017"]}]},{"name":"Italian Ministry of Health","award":["PRIN 2022"],"award-info":[{"award-number":["PRIN 2022"]}]},{"name":"Italian Ministry of Health","award":["PNRR-MCNT2-2023-12378122"],"award-info":[{"award-number":["PNRR-MCNT2-2023-12378122"]}]},{"name":"Italian Ministry of Health","award":["PNRR-MAD-2022-12375909"],"award-info":[{"award-number":["PNRR-MAD-2022-12375909"]}]},{"DOI":"10.13039\/501100003196","name":"Ricerca Finalizzata 2018","doi-asserted-by":"publisher","award":["PRIN 2022 PNRR"],"award-info":[{"award-number":["PRIN 2022 PNRR"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ricerca Finalizzata 2018","doi-asserted-by":"publisher","award":["PRIN 2017"],"award-info":[{"award-number":["PRIN 2017"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ricerca Finalizzata 2018","doi-asserted-by":"publisher","award":["PRIN 2022"],"award-info":[{"award-number":["PRIN 2022"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ricerca Finalizzata 2018","doi-asserted-by":"publisher","award":["PNRR-MCNT2-2023-12378122"],"award-info":[{"award-number":["PNRR-MCNT2-2023-12378122"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ricerca Finalizzata 2018","doi-asserted-by":"publisher","award":["PNRR-MAD-2022-12375909"],"award-info":[{"award-number":["PNRR-MAD-2022-12375909"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Growing evidence attests to the multifaceted roles of group 2 innate lymphoid cells (ILC2s) in cancer immunity. They exhibit either pro- or anticancer activity depending on tumor type but their function in Multiple Myeloma (MM) is still not elucidated. Methods: The bone marrow (BM) and peripheral blood (PB) of patients (pts) with MM or precancerous conditions were collected, and specific properties of ILC2 subsets were assessed by flow cytometry. Results: By dissecting ILC2s according to c-Kit marker, we observed that NKp30 and NKG2D were mainly confined to c-Kithi ILC2s, while levels of DNAM-1 was significantly higher in fully mature c-Kitlo cells. Among the total MM-associated ILC2s (MM-ILC2s), we observed a significant increase in c-the Kitlo subset, but the expression of DNAM-1 in these cells was significantly reduced, especially in BM. Interestingly, MM-ILC2s from PB expressed granzyme B (GZMB), but its expression was impaired in BM-ILC2s. Accordingly, MM cells were susceptible to killing by MM-ILC2s derived from PB while eluding ILC2 surveillance in BM. Indeed, in MM-ILC2s derived from BM, the downregulation of DNAM-1 is accompanied by the upregulation of TIGIT, which mediate cell death in ILC2s upon recognition of the cognate ligands expressed by MM cells. These ILC2 changes appeared in clinical precursor conditions and eventually accumulated with disease progression. Conclusions: MM-ILC2s can act as cytolytic immune effectors that are fully competent in PB. However, MM cells shift ILC2 fate towards cell death in BM via the upregulation of TIGIT, thereby representing a potential therapeutic target to restore ILC2 antitumor activity.<\/jats:p>","DOI":"10.3390\/cancers17020263","type":"journal-article","created":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T04:42:08Z","timestamp":1736916128000},"page":"263","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Multiple Myeloma Cells Shift the Fate of Cytolytic ILC2s Towards TIGIT-Mediated Cell Death"],"prefix":"10.3390","volume":"17","author":[{"given":"Fabiana","family":"Drommi","sequence":"first","affiliation":[{"name":"Laboratory of Immunology and Biotherapy, Department Human Pathology in Adulthood and Childhood \u201cGaetano Barresi\u201d, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"Calabr\u00f2","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology and Biotherapy, Department Human Pathology in Adulthood and Childhood \u201cGaetano Barresi\u201d, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaetana","family":"Pezzino","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology and Biotherapy, Department Human Pathology in Adulthood and Childhood \u201cGaetano Barresi\u201d, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grazia","family":"Vento","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine (DIMES), University of Genoa, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e8","family":"Freni","sequence":"additional","affiliation":[{"name":"Laboratory of Histology, Department of Biomedical, Dental, Morphological and Functional Imaging Sciences, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregorio","family":"Costa","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology and Biotherapy, Department Human Pathology in Adulthood and Childhood \u201cGaetano Barresi\u201d, University of Messina, 98125 Messina, Italy"},{"name":"Clinical Pathology Unit, University Hospital Policlinico \u201cG. Martino\u201d, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Cavaliere","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology and Biotherapy, Department Human Pathology in Adulthood and Childhood \u201cGaetano Barresi\u201d, University of Messina, 98125 Messina, Italy"},{"name":"Clinical Pathology Unit, University Hospital Policlinico \u201cG. Martino\u201d, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Bonaccorsi","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology and Biotherapy, Department Human Pathology in Adulthood and Childhood \u201cGaetano Barresi\u201d, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6156-8239","authenticated-orcid":false,"given":"Alessandro","family":"Allegra","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Human Pathology in Adulthood and Childhood \u201cGaetano Barresi\u201d, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Ferlazzo","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine (DIMES), University of Genoa, 16132 Genova, Italy"},{"name":"Unit of Experimental Pathology and Immunology, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"De Pasquale","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology and Biotherapy, Department Human Pathology in Adulthood and Childhood \u201cGaetano Barresi\u201d, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Campana","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology and Biotherapy, Department Human Pathology in Adulthood and Childhood \u201cGaetano Barresi\u201d, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.coi.2013.02.010","article-title":"Development and function of group 2 innate lymphoid cells","volume":"25","author":"Walker","year":"2013","journal-title":"Curr. 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