CLOCK and cancer: For instance, in GBM, high levels of CLOCK in GSCs are associated with an increase in microglia in TME, mediated by the transcriptional regulation of chemokine-like protein 3.225 The deficiency of Bmal1 in melanoma cells also impacts immunocytes within TME, including CD8+ T cells and TAMs.231 In kidney clear cell carcinoma (KIRC) and breast cancer, the expression of clock genes (such as CLOCK, BMAL1, and PER3) in cancer cells exhibits rhythmic fluctuations.