SYNPO and neoplasm: Intriguingly, the PD-L2 and TIM3 were significantly higher in non-responsive tumor, suggesting that upregulations of other corresponding or bypass checkpoint pathway may contribute to the resistance of PD-1 blockades (figure 2B–D and online supplemental table S5), by which according to reports the stromal activation and T-cell exclusion were induced.6 Additionally, SYNPO was reported to be upregulated during CAF activation,45 which is the critical mechanism of ICB resistance.