biostudies-literatureMa WHNational Natural Science Foundation of ChinaNational Natural Science Foundation of China (National Science Foundation of China)72-93https://www.ebi.ac.uk/biostudies/studies/S-EPMC12765898biostudies-literatureUnknown36(1)Colorectal cancer (CRC) remains largely refractory to immune-checkpoint blockade, with adenomatous polyposis coli (APC) mutations present in 80%-90% of cases. Loss of APC was previously thought to promote tumor progression mainly through deregulated Wnt/β-catenin signaling. Here, we report that APC loss leads to inhibition of CD8⁺ T cell infiltration and CRC immune evasion through the dephosphorylation of signal transducers and activators of transcription 1 (STAT1) by protein tyrosine phosphatase non-receptor type 13 (PTPN13), independently of β-catenin. Peptides containing the last 11 C-terminal amino acid (aa) residues of APC (APC11) bind directly to PTPN13 to block PTPN13-STAT1 interactions and facilitate STAT1 phosphorylation, interferon regulatory factor-1 (IRF1) expressionCell researchTargeting PTPN13 with 11-amino-acid peptides of C-terminal APC prevents immune evasion of colorectal cancer.PMC1276589882441036Li GJing LZhou WJLiu HJShen RFLuo TYWu DLi KSun XWu ZKBai XQiu XMa WHHe YMou TXu ZLGao YLi WYChen YHWang LJWang WChen TfalseTargeting PTPN13 with 11-amino-acid peptides of C-terminal APC prevents immune evasion of colorectal cancer.Colorectal cancer (CRC) remains largely refractory to immune-checkpoint blockade, with adenomatous polyposis coli (APC) mutations present in 80%-90% of cases. Loss of APC was previously thought to promote tumor progression mainly through deregulated Wnt/β-catenin signaling. Here, we report that APC loss leads to inhibition of CD8⁺ T cell infiltration and CRC immune evasion through the dephosphorylation of signal transducers and activators of transcription 1 (STAT1) by protein tyrosine phosphatase non-receptor type 13 (PTPN13), independently of β-catenin. Peptides containing the last 11 C-terminal amino acid (aa) residues of APC (APC11) bind directly to PTPN13 to block PTPN13-STAT1 interactions and facilitate STAT1 phosphorylation, interferon regulatory factor-1 (IRF1) expression2026-01-01T00:00:00Z2026 Jan2026-06-06T20:03:15.346Z2026-06-04T03:14:49.679ZS-EPMC127658984148629310.1038/s41422-025-01206-4