Variations in Hes1 nuclear/cytoplasmic localization influence its function, and the absence of nuclear expression may induce an immunosuppressive microenvironment by activating the IL6/IL10 pathway (138); dynamic regulation of Hes1 function is mediated by factors such as autonomous oscillatory expression characteristics (21) and the involvement of regulatory factors like RIP140; inherent differences in Notch signaling activity and microsatellite status may exist between right-sided and left-sided CRC (138, 150). Here, HES1 is linked to colorectal carcinoma.