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However, whether disease- and therapy-related alterations in immune cells and cytokine-responsiveness contribute to the observed heterogeneous vaccination responses is unclear. Thus, we analyzed peripheral blood mononuclear cells from patients with MM during and after SARS-CoV-2 vaccination and breakthrough infection (BTI) using combined whole-transcriptome and surface proteome single-cell profiling with functional serological and T-cell validation in 58 MM patients. Our results demonstrate that vaccine-responders showed a significant overrepresentation of cytotoxic CD4<jats:sup>+<\/jats:sup> T- and mature CD38<jats:sup>+<\/jats:sup> NK-cells expressing FAS<jats:sup>+<\/jats:sup>\/TIM3<jats:sup>+<\/jats:sup> with a robust cytokine-responsiveness, such as type-I-interferon-, IL-12- and TNF-\u03b1-mediated signaling. Patients with MM experiencing BTI developed strong serological and cellular responses and exhibited similar cytokine-responsive immune cell patterns as vaccine-responders. This study can expand our understanding of molecular and cellular patterns associated with immunization responses and may benefit the design of improved vaccination strategies in immunocompromised patients.<\/jats:p>","DOI":"10.1038\/s41375-023-02070-0","type":"journal-article","created":{"date-parts":[[2023,12,4]],"date-time":"2023-12-04T12:02:34Z","timestamp":1701691354000},"page":"168-180","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Cytokine-responsive T- and NK-cells portray SARS-CoV-2 vaccine-responders and infection in multiple myeloma patients"],"prefix":"10.1038","volume":"38","author":[{"given":"Julius C.","family":"Enssle","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9290-9697","authenticated-orcid":false,"given":"Julia","family":"Campe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina","family":"Moter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Voit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alec","family":"Gessner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijia","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Wolf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bj\u00f6rn","family":"Steffen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hubert","family":"Serve","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Bremm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Huenecke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Lohoff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Vehreschild","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger F.","family":"Rabenau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5417-9307","authenticated-orcid":false,"given":"Marek","family":"Widera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Ciesek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6570-6125","authenticated-orcid":false,"given":"Thomas","family":"Oellerich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Imkeller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4158-5872","authenticated-orcid":false,"given":"Michael A.","family":"Rieger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana","family":"von Metzler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8530-1192","authenticated-orcid":false,"given":"Evelyn","family":"Ullrich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,12,4]]},"reference":[{"key":"2070_CR1","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/s41375-020-01016-0","volume":"35","author":"H Ludwig","year":"2021","unstructured":"Ludwig H, Boccadoro M, Moreau P, San-Miguel J, Cavo M, Pawlyn C, et al. 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IvM received honoraria for advising Pfizer, Sanofi, BMS, GSK, Amgen, Janssen, Takeda and AstraZeneca. EU received honoraria for advising Phialogics and BMS. MW has received speaker fees from AstraZeneca. All other authors declare no competing interests to the present study.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}