• Treatment options for relapsed/refractory PMBCL are limited, and prognosis is generally poor.• Pembrolizumab had a manageable safety profile and promising antitumor activity in heavily pretreated rrPMBCL patients.Treatment options for relapsed/refractory primary mediastinal large B-cell lymphoma (rrPMBCL) are limited, and prognosis is generally poor (overall response rate [ORR] 0% to 25%; 2-year overall survival 15%). PMBCL frequently involves PD-1 ligand overexpression, potentially making PMBCL particularly susceptible to PD-1 blockade. We evaluated safety and antitumor activity of pembrolizumab, an anti-PD-1 antibody, in rrPMBCL as part of the KEYNOTE-013 multicohort phase 1b trial. At time of data cutoff, 18 patients (median age 30 years; median 3 prior lines of therapy) had been enrolled and treated, of whom 17 were included in the efficacy analyses. Eleven patients (61%) experienced drug-related adverse events (mostly grade 1-2); none discontinued treatment due to adverse events. ORR was 41% (7/17); 6 additional patients (35%) had stable disease. Of patients evaluable by imaging, 13 out of 16 (81%) had decreases in target lesions. With a median follow-up of 11.3 months, median duration of response was not reached. Two patients reached the maximum 2-year treatment duration and remain in remission. Median overall survival was not reached for treated patients overall; all responders were still alive at data cutoff. These results in heavily pretreated rrPMBCL patients demonstrate that PD-1 blockade with pembrolizumab has a manageable safety profile and promising antitumor activity. This trial was registered at www.clinicaltrials.gov as #NCT01953692. (Blood. 2017;130(3):267-270)
We investigated the influence of the macrophage iron exporter ferroportin and its ligand hepcidin on intracellular Salmonella growth. Elevated ferroportin expression inhibited bacterial multiplication; hepcidininduced ferroportin down-regulation enhanced it. Expression analysis of iron-responsive Salmonella genes indicated ferroportin-mediated iron deprivation. These results demonstrate a role for ferroportin in antimicrobial resistance.
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