Our recent studies indicate that NHE1 protein is involved in regulating GBM immunosuppressive TME because combining anti-PD-1 immune checkpoint blockade with NHE1 inhibitor HOE642 with or without TMZ therapy increased immunity in an immunogenic mouse syngeneic intracranial GBM model 14, 15. The gene discussed is PDCD1; the disease is glioblastoma.