E-resources
Peer reviewed
Open access
-
Toffalori, Cristina; Zito, Laura; Gambacorta, Valentina; Riba, Michela; Oliveira, Giacomo; Bucci, Gabriele; Barcella, Matteo; Spinelli, Orietta; Greco, Raffaella; Crucitti, Lara; Cieri, Nicoletta; Noviello, Maddalena; Manfredi, Francesco; Montaldo, Elisa; Ostuni, Renato; Naldini, Matteo M; Gentner, Bernhard; Waterhouse, Miguel; Zeiser, Robert; Finke, Jurgen; Hanoun, Maher; Beelen, Dietrich W; Gojo, Ivana; Luznik, Leo; Onozawa, Masahiro; Teshima, Takanori; Devillier, Raynier; Blaise, Didier; Halkes, Constantijn J M; Griffioen, Marieke; Carrabba, Matteo G; Bernardi, Massimo; Peccatori, Jacopo; Barlassina, Cristina; Stupka, Elia; Lazarevic, Dejan; Tonon, Giovanni; Rambaldi, Alessandro; Cittaro, Davide; Bonini, Chiara; Fleischhauer, Katharina; Ciceri, Fabio; Vago, Luca
Nature medicine, 04/2019, Volume: 25, Issue: 4Journal Article
Transplantation of hematopoietic cells from a healthy individual (allogeneic hematopoietic cell transplantation (allo-HCT)) demonstrates that adoptive immunotherapy can cure blood cancers: still, post-transplantation relapses remain frequent. To explain their drivers, we analyzed the genomic and gene expression profiles of acute myeloid leukemia (AML) blasts purified from patients at serial time-points during their disease history. We identified a transcriptional signature specific for post-transplantation relapses and highly enriched in immune-related processes, including T cell costimulation and antigen presentation. In two independent patient cohorts we confirmed the deregulation of multiple costimulatory ligands on AML blasts at post-transplantation relapse (PD-L1, B7-H3, CD80, PVRL2), mirrored by concomitant changes in circulating donor T cells. Likewise, we documented the frequent loss of surface expression of HLA-DR, -DQ and -DP on leukemia cells, due to downregulation of the HLA class II regulator CIITA. We show that loss of HLA class II expression and upregulation of inhibitory checkpoint molecules represent alternative modalities to abolish AML recognition from donor-derived T cells, and can be counteracted by interferon-γ or checkpoint blockade, respectively. Our results demonstrate that the deregulation of pathways involved in T cell-mediated allorecognition is a distinctive feature and driver of AML relapses after allo-HCT, which can be rapidly translated into personalized therapies.
Author
![loading ... loading ...](themes/default/img/ajax-loading.gif)
Shelf entry
Permalink
- URL:
Impact factor
Access to the JCR database is permitted only to users from Slovenia. Your current IP address is not on the list of IP addresses with access permission, and authentication with the relevant AAI accout is required.
Year | Impact factor | Edition | Category | Classification | ||||
---|---|---|---|---|---|---|---|---|
JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Select the library membership card:
If the library membership card is not in the list,
add a new one.
DRS, in which the journal is indexed
Database name | Field | Year |
---|
Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
---|
Source: Personal bibliographies
and: SICRIS
The material is available in full text. If you wish to order the material anyway, click the Continue button.