Matches in SemOpenAlex for { <https://semopenalex.org/work/W2914976598> ?p ?o ?g. }
Showing items 1 to 85 of
85
with 100 items per page.
- W2914976598 endingPage "3340" @default.
- W2914976598 startingPage "3340" @default.
- W2914976598 abstract "Abstract Allogeneic hematopoietic cell transplantation (HCT) is a curative treatment option for hematologic malignancies but relapse remains the most common cause of death. Infusion of donor lymphocytes (DLIs) can induce remission and prolong survival by exerting potent graft-versus-leukemia (GVL) effects. However, sufficient tumor control cannot be established in all patients. We showed previously that invariant natural killer T (iNKT) cells promote anti-tumor immunity in murine models of allogeneic HCT without exacerbating graft-versus-host disease (GVHD). We therefore studied iNKT cells in DLIs and investigated how culture-expanded iNKT cells from such DLIs (DLI-iNKTs) could lyse leukemia cells. We analyzed 63 cryopreserved DLI samples by flow cytometry. iNKT cells were identified using the PBS57-loaded CD1d tetramer. Under steady state conditions, iNKT cells represent 0.04% (range, 0.01-0.6) of live donor lymphocytes and need to undergo ex vivo expansion for further experiments and clinical application. We established a two-week protocol resulting in a 300-fold expansion of functional DLI-iNKTs with a purity of 94%. Interestingly, we observed a preferential expansion of CD4+ DLI-iNKTs. This subset turned out to be critical for tolerance induction and prevention of GVHD after allogeneic HCT. For degranulation and leukemia cell lysis assays, culture-expanded DLI-iNKTs were co-cultured with leukemia cells. CD107a as a marker of degranulation and iNKT-cell activity was upregulated on DLI-iNKTs upon engagement with leukemia cells that were subsequently lysed in a dose-dependent manner. We also observed an increased release of cytokines like IFN-γ (85 vs. 7 pg/ml, p=0.04). Moreover, the cytotoxic effects of culture-expanded DLI-iNKTs were CD1d-dependent: blocking the interaction between the MHC-I-like molecule CD1d and the T-cell receptor of DLI-iNKTs abrogated iNKT-cell degranulation and efficient leukemia cell lysis. Our results suggest that iNKT cells from DLIs are involved in anti-tumor immunity after allogeneic HCT and therefore may reduce the risk of relapse and improve progression-free and overall survival. Prior expansion of iNKT cells could promote beneficial effects on tumor control, immune tolerance and overall survival. Disclosures Handgretinger: Miltenyi Biotec: Patents & Royalties: Co-patent holder of TcR alpha/beta depletion technologies, Research Funding. Bethge:Miltenyi Biotec GmbH: Consultancy, Honoraria, Research Funding; Neovii GmbH: Honoraria, Research Funding." @default.
- W2914976598 created "2019-02-21" @default.
- W2914976598 creator A5018999978 @default.
- W2914976598 creator A5023183268 @default.
- W2914976598 creator A5024956673 @default.
- W2914976598 creator A5025561569 @default.
- W2914976598 creator A5035626095 @default.
- W2914976598 creator A5040611256 @default.
- W2914976598 creator A5065062556 @default.
- W2914976598 creator A5065785815 @default.
- W2914976598 creator A5066624700 @default.
- W2914976598 creator A5075561674 @default.
- W2914976598 creator A5090207072 @default.
- W2914976598 creator A5091041569 @default.
- W2914976598 date "2018-11-29" @default.
- W2914976598 modified "2023-10-01" @default.
- W2914976598 title "Invariant Natural Killer T Cells from Donor Lymphocyte Infusions (DLI-iNKTs) Contribute to Anti-Tumor Immunity after Allogeneic Hematopoietic Cell Transplantation" @default.
- W2914976598 doi "https://doi.org/10.1182/blood-2018-99-111745" @default.
- W2914976598 hasPublicationYear "2018" @default.
- W2914976598 type Work @default.
- W2914976598 sameAs 2914976598 @default.
- W2914976598 citedByCount "0" @default.
- W2914976598 crossrefType "journal-article" @default.
- W2914976598 hasAuthorship W2914976598A5018999978 @default.
- W2914976598 hasAuthorship W2914976598A5023183268 @default.
- W2914976598 hasAuthorship W2914976598A5024956673 @default.
- W2914976598 hasAuthorship W2914976598A5025561569 @default.
- W2914976598 hasAuthorship W2914976598A5035626095 @default.
- W2914976598 hasAuthorship W2914976598A5040611256 @default.
- W2914976598 hasAuthorship W2914976598A5065062556 @default.
- W2914976598 hasAuthorship W2914976598A5065785815 @default.
- W2914976598 hasAuthorship W2914976598A5066624700 @default.
- W2914976598 hasAuthorship W2914976598A5075561674 @default.
- W2914976598 hasAuthorship W2914976598A5090207072 @default.
- W2914976598 hasAuthorship W2914976598A5091041569 @default.
- W2914976598 hasBestOaLocation W29149765981 @default.
- W2914976598 hasConcept C109159458 @default.
- W2914976598 hasConcept C126322002 @default.
- W2914976598 hasConcept C170493617 @default.
- W2914976598 hasConcept C203014093 @default.
- W2914976598 hasConcept C2777408962 @default.
- W2914976598 hasConcept C2778461978 @default.
- W2914976598 hasConcept C2779695342 @default.
- W2914976598 hasConcept C28328180 @default.
- W2914976598 hasConcept C2911091166 @default.
- W2914976598 hasConcept C49802076 @default.
- W2914976598 hasConcept C502942594 @default.
- W2914976598 hasConcept C71924100 @default.
- W2914976598 hasConcept C86803240 @default.
- W2914976598 hasConcept C95444343 @default.
- W2914976598 hasConceptScore W2914976598C109159458 @default.
- W2914976598 hasConceptScore W2914976598C126322002 @default.
- W2914976598 hasConceptScore W2914976598C170493617 @default.
- W2914976598 hasConceptScore W2914976598C203014093 @default.
- W2914976598 hasConceptScore W2914976598C2777408962 @default.
- W2914976598 hasConceptScore W2914976598C2778461978 @default.
- W2914976598 hasConceptScore W2914976598C2779695342 @default.
- W2914976598 hasConceptScore W2914976598C28328180 @default.
- W2914976598 hasConceptScore W2914976598C2911091166 @default.
- W2914976598 hasConceptScore W2914976598C49802076 @default.
- W2914976598 hasConceptScore W2914976598C502942594 @default.
- W2914976598 hasConceptScore W2914976598C71924100 @default.
- W2914976598 hasConceptScore W2914976598C86803240 @default.
- W2914976598 hasConceptScore W2914976598C95444343 @default.
- W2914976598 hasIssue "Supplement 1" @default.
- W2914976598 hasLocation W29149765981 @default.
- W2914976598 hasOpenAccess W2914976598 @default.
- W2914976598 hasPrimaryLocation W29149765981 @default.
- W2914976598 hasRelatedWork W2086149900 @default.
- W2914976598 hasRelatedWork W2174188437 @default.
- W2914976598 hasRelatedWork W2348031615 @default.
- W2914976598 hasRelatedWork W2357142827 @default.
- W2914976598 hasRelatedWork W2376376709 @default.
- W2914976598 hasRelatedWork W2386230525 @default.
- W2914976598 hasRelatedWork W2414647507 @default.
- W2914976598 hasRelatedWork W2944683649 @default.
- W2914976598 hasRelatedWork W4210379329 @default.
- W2914976598 hasRelatedWork W4309728627 @default.
- W2914976598 hasVolume "132" @default.
- W2914976598 isParatext "false" @default.
- W2914976598 isRetracted "false" @default.
- W2914976598 magId "2914976598" @default.
- W2914976598 workType "article" @default.