Simple Summary Perinatal and early-life factors have been hypothesized to influence non-Hodgkin lymphoma (NHL) risk, but study results have been mixed and exposure data for childhood ages are limited. In this case–control study of 2280 NHL cases and 2253 controls, we assessed perinatal and early-life factors in association with risk of developing NHL later in life. Greater weight at birth, in childhood, and in late adolescence were all associated with greater risk of NHL. Breastfeeding duration of >6 months compared to never being breastfed was inversely associated with NHL risk. We did not observe any statistically significant associations for other perinatal and early life factors evaluated, and overall associations did not substantively vary by major NHL subtype. Excess body weight across the life course, including in early life, may influence risk of developing NHL later in life.
G. Cholack, G. Kleinstern, Dennis P. Robinson et al.· Cancers· 0 citations
Germinal center (GC)-derived lymphomas arise within a specialized immune ecosystem, yet whether malignant cells direct its remodeling remains unclear. Integrating genomic, transcriptomic, spatial, and functional analyses across follicular lymphoma and diffuse large B-cell lymphoma, we define a developmental framework linking malignant B-cell differentiation state to tumor microenvironment (TME) organization. Rather than segregating by histology, lymphomas align along a shared differentiation continuum in which proliferative dark zone (DZ) states associate with immune-depleted TMEs, whereas post-GC/memory B-cell (MBC) states drive inflamed but immunosuppressed TMEs. Spatial profiling reveals collapse of GC architecture and emergence of suppressive myeloid niches along this trajectory. Single-cell lineage reconstruction uncovers a DZ-to-MBC developmental axis underlying lymphoma evolution. Genetic reprogramming in vivo demonstrates that malignant differentiation state is sufficient to instruct TME remodeling. Collectively, these findings establish malignant differentiation state as a causal determinant of immune architecture across GC-derived lymphomas and identify lineage-directed immune reprogramming as a potential therapeutic strategy.
P. Mondello, A. Sadekova, ksenia fede et al.· Research Square· 0 citations
