The DOI matches its Crossref record; 51 of the 51 references it cites were found in a registry or an index.
Immune signature drives leukemia escape and relapse after hematopoietic cell transplantation
Open accessAbstract
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. Post-transplantation relapse in acute myeloid leukemia patients without genomic loss of HLA is driven by transcriptional alterations in antigen presentation and T cell costimulation genes.
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Self-citationImmune escape and immunotherapy of acute myeloid leukemia
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Metadata
- Authors
- Toffalori, C., Zito, L., Gambacorta, V., Riba, M., Oliveira, G., Bucci, G., Barcella, M., Spinelli, O., Greco, R., Crucitti, L., Cieri, N., Noviello, M., Manfredi, F., Montaldo, E., Ostuni, R., Naldini, M. M., Gentner, B., Waterhouse, M., Zeiser, R., Finke, J., Hanoun, M., Beelen, D. W., Gojo, I., Luznik, L., Onozawa, M., Teshima, T., Devillier, R., Blaise, D., Halkes, C. J. M., Griffioen, M., Carrabba, M. G., Bernardi, M., Peccatori, J., Barlassina, C., Stupka, E., Lazarevic, D., Tonon, G., Rambaldi, A., Cittaro, D., Bonini, C., Fleischhauer, K., Ciceri, F., & Vago, L.
- Venue
- Nature Medicine
- Published
- 2019-03-25
- Volume
- 25
- Issue
- 4
- Pages
- 603-611
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2925256229
- Cited by
- 401
- References
- 51
- FWCI
- 29.16
- Type
- journal article
- Language
- en
- Open access
- green
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- Toffalori, C., Zito, L., Gambacorta, V., Riba, M., Oliveira, G., Bucci, G., Barcella, M., Spinelli, O., Greco, R., Crucitti, L., Cieri, N., Noviello, M., Manfredi, F., Montaldo, E., Ostuni, R., Naldini, M. M., Gentner, B., Waterhouse, M., Zeiser, R., . . . Vago, L. (2019). Immune signature drives leukemia escape and relapse after hematopoietic cell transplantation. Nature Medicine. https://doi.org/10.1038/s41591-019-0400-z
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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