Editorial: IUIS Junior Community: Pushing the Frontiers of Immunology

Adeleye O Adeshakin^1*Anne M Hahn^2*

• ¹St Jude Children's Research Hospital, Memphis, United States
• ²Peter Doherty Institute for Infection and Immunity, Melbourne, Australia

Cruz-Cárdenas et al. report the generation of CRISPR/Cas9-engineered neutrophil-like cell lines lacking either CD16b or CD32a, overcoming a major barrier to dissecting receptor-specific FcγR signaling, cytokine regulation, and ROS generation in neutrophils. By establishing CD16b -/-and CD32a -/-promyelocytic lines that differentiate into neutrophil-like cells, they provide a donor-independent platform to interrogate FcγR function, revealing distinct cytokine signatures and offering a powerful genetic system for mechanistic immunology and therapeutic Fc engineering (1). Information System® /monoclonal Antibodies (IMGT/mAb)-Knowledge Graph (IMGT/mAb-KG), a structured, interoperable graph that integrates therapeutic monoclonal antibody data with IMGT genomic and structural resources (2). This resource, comprising over 100,000 triples and covering nearly 1,500 mAbs, hundreds of targets and indications, and about 40,000 of study products. It enables sophisticated, cross-cutting queries on constructs, clinical development, mechanisms of action, and paratope-epitope relationships, thereby providing a robust informatics substrate for computational immunology and mAb discovery workflows.Mentuci et al. present a comprehensive review of how cancer-associated fibroblasts (CAFs) impair dendritic cell (DC) biology across solid tumors, framing CAF-DC crosstalk as a key stromal axis of immune escape and a promising target for next-generation immunotherapy. By integrating DC subset biology with tumor microenvironment remodeling, they show how CAF-driven DC dysfunction skews adaptive immunity toward tolerance and regulatory phenotypes (3). They further proposed that effective restoration of DC function will require combined DC-targeted strategies and stromal/CAF reprogramming to improve responses to vaccines, checkpoint blockade, and radiotherapy. Ruffinatto et al. review evidence positioning hematopoietic stem cells (HSCs) as a central reservoir of innate immune memory, emphasizing early hematopoiesis with myeloid bias as a key determinant of long-term innate responses to infectious and inflammatory challenges (4). By synthesizing data on how cytokines, Pathogen-Associated Molecular Patterns (PAMPs), pathogens, and vaccines imprint HSCs, they link specific inflammatory environment to durable changes in lineage bias, function, and HSC exhaustion. Thus, propose that targeted modulation of "HSC training" could be exploited to enhance protective trained immunity or to mitigate maladaptive inflammatory memory in chronic disease and transplantation contexts (5). China to identify differences in infections with or without vaccination via regression modelling. They found that breakthrough infections were more likely to occur after receiving one vaccine dose and in the youngest age group. Their findings highlight the reduction of vaccine breakthrough cases in recipients of two vaccine doses in line with the World Health organization's recently updated recommendations (6). They also point out the need to explore potential benefits of further booster vaccinations. Mechanistic insights into such questions could benefit from serological and laboratory analysis to further improve our understanding on how vaccination shapes disease transmission dynamics (7).Taken together, this first IUIS Junior Community Research Topic showcases impactful advances by early-career immunologists in cellular engineering, immunoinformatics, tumor immunology, stem cellbased innate immune memory and epidemiology, while acknowledging that many additional breakthroughs from junior investigators remain to be captured. Building on this momentum, submissions are now welcomed for "IUIS Junior Community: Research Topic -Volume II," which aims to further amplify the scientific voice and visibility of the next generation of immunologists. While our IUIS Junior Community continues to grow, we hope for even more geographical and topical diversity for the next submissions and continue highlighting the excellent work that is done by immunologists around the world.