Likewise, another difficulty for the efficacy of this therapeutic treatment in GBM is the T cells exhaustion and the presence of alternative immune checkpoints, such as TIM3, LAG3, BTLA, CD244, CD160, CD39 or TIGIT, which lead to a state of terminal exhaustion that cannot be reversed solely by traditional immune checkpoint blockade (Fig. 2). The gene discussed is ENTPD1; the disease is glioblastoma.