Immune checkpoints PVR and PVRL2 are prognostic markers in AML and their blockade represents a new therapeutic option.

ABSTRACT: Immune checkpoints are promising targets in cancer therapy. Recently, poliovirus receptor (PVR) and poliovirus receptor-related 2 (PVRL2) have been identified as novel immune checkpoints. In this investigation we show that acute myeloid leukemia (AML) cell lines and AML patient samples highly express the T-cell immunoreceptor with Ig and ITIM domains (TIGIT) ligands PVR and PVRL2. Using two independent patient cohorts, we could demonstrate that high PVR and PVRL2 expression correlates with poor outcome in AML. We show for the first time that antibody blockade of PVR or PVRL2 on AML cell lines or primary AML cells or TIGIT blockade on immune cells increases the anti-leukemic effects mediated by PBMCs or purified CD3⁺ cells in vitro. The cytolytic activity of the BiTE® antibody co

SUBMITTER: Stamm H 

PROVIDER: S-EPMC6160395 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature