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Elucidating pathways that enhance GSC properties and determine their cell-specific interactions within the immunosuppressive GBM microenvironment are critical for developing effective therapeutic approaches. The CLOCK-BMAL1 complex, which is well known for its activity as a circadian rhythm\u2013regulating transcription factor, plays a critical role in maintaining GSC stemness, and the gene encoding CLOCK was found to be amplified in about 5% of GBM cases. Here, Zhou et al. have uncovered a \u201csymbiotic exclusivity\u201d relationship between CLOCK-BMAL1 and TFPI2, which is also amplified in a small proportion of GBM cases. This relationship forms a HIF-1\u03b1\/NF-\u03baB P65\u2013mediated positive feedback loop that boosts the proliferative and tumor-enhancing capacities of GSC and immunosuppressive microglia. This self-amplifying regulatory circuit represents an opportunity for intervention to inhibit GBM growth.<\/jats:p>","DOI":"10.1172\/jci205841","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T15:50:37Z","timestamp":1779205837000},"source":"Crossref","is-referenced-by-count":2,"title":["Uncovering a feedback loop in glioblastoma that reinforces stemness and immunosuppression"],"prefix":"10.1172","volume":"136","author":[{"given":"Petros","family":"Basakis","sequence":"first","affiliation":[{"name":"Department of Pathology, Northwestern Medicine Malnati Brain Tumor Institute of the Robert H. 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