Issue Archive

Neutrophils are important mediators of inflammation and play an increasingly accepted role in altering immune responses. This excellent review by Moffatt and Gwyer Findlay summarizes the current knowledge on T-cell–neutrophil interactions in tissues and lymph nodes. The authors highlight discrepancies between mice and humans and identify key areas where more research is needed to understand the importance of antigen presentation by neutrophils in humans.

The ZUMA-7 trial demonstrated superiority of the CD19-directed chimeric antigen receptor T-cell therapy axicabtagene ciloleucel (axi-cel) over prior standard-of-care (SOC) chemotherapy with autologous stem cell transplant for second-line treatment of early relapse or refractory large B-cell lymphoma. Locke et al analyzed outcomes of patients in this trial by metabolic tumor volume (MTV), showing that MTV was prognostic of responses in both arms and that axi-cel was superior to prior SOC in patients with either high or low MTV. These data help risk stratify patients prospectively for both efficacy and chance of experiencing neurotoxicity or cytokine release syndrome.

Interferon alfa (IFN-α) can induce deep molecular remissions in some patients with the myeloproliferative neoplasms (MPNs) polycythemia vera and essential thrombocythemia harboring JAK2-V617F, but resistance can emerge. Usart et al report compelling evidence from mouse models and human cells that heterozygous and homozygous deletion of Dnmt3a prevents the hematopoietic stem cell exhaustion observed with IFN-α treatment of JAK2-V617F MPNs. Loss-of-function DNMT3a mutations allow increased self-renewal of JAK2-V617F stem cells, explaining the resistance to IFN-α therapy in MPN patients with DNMT3A-mutated disease.

Wiskott-Aldrich syndrome (WAS) is an X-linked monogenic inborn error of immunity characterized by thrombocytopenia, eczema, recurrent infections, autoimmunity, and cancer risk. In a tour de force, Vallée and colleagues describe the genetic landscape affecting the WAS gene across 577 patients and resolve the associations between specific gain- or loss-of-function mutations and the severity of clinical phenotype. Class I mutations portended less severe disease while class II mutations predicted earlier onset and more severe disease with worse survival, allowing personalized prognostic advice and informing tailored care.

Nemkov et al used an interdisciplinary approach incorporating omics analyses, animal models, and genome-wide association studies to probe the genetic factors that influence cellular metabolism during red blood cell (RBC) aging. The authors identified L-carnitine metabolism as the most reproducible pathway involved across multiple blood donations and highlighted a link between this pathway, ex vivo aging of RBCs during storage, in vivo aging of RBCs in circulation, genetic polymorphisms, and clinical impact after transfusion. Their work suggests a potential new strategy to improve red cell storage quality.

In selecting individual allogeneic transplantation plans for patients, considerations about graft-versus-host disease (GVHD) prophylaxis and donor choice interact. With increasing use of posttransplant cyclophosphamide (PTCy) as GVHD prophylaxis, Sanz et al retrospectively analyzed data from patients with acute myeloid leukemia in remission who underwent allograft from unrelated donors and show that among PTCy-treated patients, donor age, not HLA disparity, was the most important predictor for survival after transplantation. These findings will help refine our approaches in selecting the right type of GVHD prophylaxis and optimal donor for patients.

Hyperhemolysis is a life-threatening complication of sickle cell disease (SCD). Nguyen and colleagues utilized in vitro and in vivo models of hyperhemolysis to demonstrate that microparticles from red blood cells lead to the same type of endothelial injury observed in other severe complications of SCD. The authors reveal the novel ability of carbon monoxide–releasing molecule CORM-401 to reduce hemolysis-induced endothelial injury and organ damage, providing a possible future treatment strategy for hyperhemolysis-associated SCD complications.