However, interactions can already occur at the level of drug absorption,27,28 eg, as recently suggested for palbociclib in patients with breast cancer.29 PPIs, by virtue of their action, also have profound effects on the microbiome, which in turn is relevant not only to the efficacy of immunotherapy, but potentially also natural immune responses to cancer.30 The most convincing hypothesis to explain the negative outcome associations in patients with glioblastoma reported here remains the activation of ALDH1A1 conferred by some PPIs (eAppendix 2 in Supplement 1).9,11. This evidence concerns the gene ALDH1A1 and glioblastoma.