Research into checkpoint markers within glioblastoma microenvironments has revealed significant differences in marker expression under varying oxygen conditions. A study identified that in hypoxic conditions, markers such as CD44, Beta-catenin, and B7-H3 were notably upregulated, while VISTA, CD56, KI-67, CD68, and CD11c showed downregulation. This differential expression highlights the adaptive mechanisms glioblastoma cells may employ to survive and proliferate in adverse conditions. The findings regarding CD44 and VISTA were further corroborated by RNA sequencing data from the Ivy GAP database, indicating a robust validation of these markers in glioblastoma pathology (ref: Petterson doi.org/10.1111/bpa.13111/). Immunohistochemical staining and digital quantification in an independent cohort confirmed the upregulation of CD44, B7-H3, and VISTA, reinforcing their potential as therapeutic targets and biomarkers for glioblastoma progression. The implications of these findings suggest that targeting these checkpoint markers could enhance treatment efficacy in glioblastoma patients, particularly in hypoxic tumor regions.