PD-1H/VISTA mediates immune evasion in acute myeloid leukemia.

Acute myeloid leukemia (AML) presents a pressing medical need in that it is largely resistant to standard chemotherapy as well as modern therapeutics, such as targeted therapy and immunotherapy, including anti-programmed cell death protein (anti-PD) therapy. We demonstrate that programmed death-1 homolog (PD-1H), an immune coinhibitory molecule, is highly expressed in blasts from the bone marrow of AML patients, while normal myeloid cell subsets and T cells express PD-1H. In studies employing syngeneic and humanized AML mouse models, overexpression of PD-1H promoted the growth of AML cells, mainly by evading T cell-mediated immune responses. Importantly, ablation of AML cell-surface PD-1H by antibody blockade or genetic knockout significantly inhibited AML progression by promoting T cell activity. In addition, the genetic deletion of PD-1H from host normal myeloid cells inhibited AML progression, and the combination of PD-1H blockade with anti-PD therapy conferred a synergistic antileukemia effect. Our findings provide the basis for PD-1H as a potential therapeutic target for treating human AML.

Prognostic factors in Tumefactive demyelinating lesions: A retrospective study.

INTRODUCTION: Demyelinating lesions occasionally present as mass-like lesions on imaging, raising concern for malignancy. The disease course of such tumefactive demyelinating lesions (TDLs) is still being defined. METHODS: We retrospectively analyzed 21 patients with new-onset neurologic symptoms and mass-like lesions on brain magnetic resonance imaging (MRI), which resulted in biopsy-proven diagnoses of demyelination. 18 patients had a median follow-up of 52 months. The clinical, radiologic and histologic features were associated with disease course. RESULTS: An aggressive disease course (ADC) was noted in 33% of the patients and was associated with an initial largest lesion size ≥35 mm (p = 0.0007), mass effect (p = 0.01) and perilesional edema (p = 0.01) on MRI. Age 30 years and older, at presentation (p = 0.05), as well as the absence of a prior tonsillectomy (p = 0.0128) were also associated with an ADC. CONCLUSIONS: We identified several factors, including initial larger lesion size, mass effect and perilesional edema on MRI, presentation after 30 years of age and the absence of a prior tonsillectomy, that predict an ADC in patients presenting with TDLs. These predictors of disease course can help guide patient follow-up and stratification for intervention.