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We previously published that hematopoietic stem cell combination therapy (HSC+aPD1) extends survival in murine CNS malignancies, including glioma. To better understand lymphoid-specific mechanisms, we analyzed various lymphoid tissues in a murine glioma model. We hypothesize early PD-1 blockade in HSCs influences later differentiation trajectories. Transferred HSCs differentiate into T-cells within the thymus and then migrate to the intracranial tumor microenvironment as anticipated. Indeed, blocking PD-1/PD-L1 signaling during HSC differentiation significantly impacts subsequent T-cell maturation. Remarkably, TILs derived from HSC^PD1KO cells were biased towards CD4⁺ Treg or CD8⁺ effector lineages, whereas HSC^PD1+/+ progeny leaned toward immature/naïve cell states.

HSCs were prepared from constitutive GFP-expressing …