Immune signature drives leukemia escape and relapse after hematopoietic cell transplantation

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-gamma 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

Decidability of modules over a Bézout domain D+XQ[X] with D a principal ideal domain and Q its field of fractions

We describe the Ziegler spectrum of a Bézout domain B = D+XQ[X] where D is a principal ideal domain and Q is its field of fractions, in particular we ccompute the Cantor-Bendixson rank of the space. Using this, we prove the decidability of the theory of B-modules when D is "sufficiently" recursive

Logic, primes and computation: a tale of unrest

The early connections between Mathematical Logic and Computer Science date back to the thirties and to the birth itself of modern Theoretical Computer Science, and concern computability. This survey wishes to emphasize how alive and fruitful this relationship has been since then, and still is

Diagnostic Performance: A Comparative Study of the Leukocyte Differential Count on Four Automated Haematology Analysers

Peer Reviewe