Using the KC mouse model of PDA, which closely recapitulates human PDA progression, Manzo et al. found that CD8 T cells acquire features of functional exhaustion: upregulation of PD-1 and TIM-3 and reduced production of IFN-γ and granzyme B. In response to the nutrient composition of the PDA TME, CD8 T cells increase the expression of the specialized lipid transporter CD36 and accumulate LCFAs. Here, GZMB is linked to Patent ductus arteriosus.