Purinergic signaling and adenosine-mediated immune regulation in hematologic malignancies

Purinergic signaling is an important regulator of immune activity in the tumor microenvironment and is increasingly relevant to hematologic malignancies. In multiple myeloma, anti-CD38 monoclonal antibodies such as daratumumab and isatuximab have transformed treatment, while raising questions about how CD38’s enzymatic activity and the wider adenosinergic network affect immune function and therapeutic response. CD38, CD39, CD203a, and CD 73 contribute to extracellular nucleotide metabolism and adenosine production, with malignant, immune, and stromal cells shaping these processes in the bone marrow niche. Extracellular vesicles may also carry purinergic enzymes or metabolites between cells. However, how these pathways vary across diseases and treatment contexts—and how they contribute to immune dysfunction, resistance, or relapse—remains incompletely understood. Advances in spatial and single-vesicle analyses offer new opportunities to investigate these mechanisms.This Research Topic aims to advance understanding of how CD38 and related purinergic and adenosinergic pathways regulate immune responses and treatment outcomes in multiple myeloma and other hematologic malignancies. It will examine how nucleotide metabolism, adenosine signaling, and interactions among malignant, immune, and stromal cells influence disease progression and therapeutic response. Contributions may investigate anti-CD38 therapy or other interventions targeting the adenosinergic axis, as well as mechanisms of resistance and potential biomarkers. By integrating mechanistic, translational, and clinical perspectives, this Research Topic seeks to identify actionable pathways and inform strategies to improve treatment response.This Research Topic focuses on purinergic signaling and immune regulation in hematologic malignancies, with an emphasis on multiple myeloma. Studies need not involve anti-CD38 therapy or extracellular vesicles; investigations of related purinergic targets and pathways are also within scope. To gather further insights into these processes, we welcome articles addressing, but not limited to, the following themes:• CD38 catalytic activity and NAD⁺ metabolism• CD39, CD73, CD203a, and adenosine receptor signaling• Purinergic regulation in the bone marrow microenvironment• Adenosine-mediated immune dysfunction• Purinergic signaling in treatment response, resistance, and relapse• Therapeutic modulation of the adenosinergic axis, including combination strategies and biomarkers• Extracellular vesicles as carriers of purinergic enzymes or metabolites• Spatial, metabolic, and single-vesicle approaches to studying purinergic pathwaysPlease note: Manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic. Topic editors: Alberto Leonardo Horenstein, Fabio Morandi Source: https://www.frontiersin.org/research-topics/87207/purinergic-signaling-and-adenosine-mediated-immune-regulation-in-hematologic-malignancies