• Intratumoral Tregs are characterized by low activity of the MondoA-thiokycin interacting protein (TXNIP) axis and increased glucose uptake.• Inhibition of the MondoA-TXNIP axis promotes glucose uptake and glycolysis, inducing Th 17-like Tregs with high glycolysis, thereby promoting Th 17 inflammation, promoting interleukin 17A-induced CD8+ T cell exhaustion, and driving colorectal cancer.• IL-17A blockers can be coordinated with PD-1 inhibitors in treating AOM-DSS-induced colorectal cancer. Here, CD8A is linked to infectious otitis media.