Volume 36, No 1, Jan 2026

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 36 Issue 1, January 2026: 72-93   |  Open Access

ORIGINAL ARTICLES

Targeting PTPN13 with 11-amino-acid peptides of C-terminal APC prevents immune evasion of colorectal cancer

Wen-Hui Ma^1,2,3,† , Wen-Yi Li^1,2,3,† , Tao Chen^1,4,† , Linqian Jing^5,† , Yue-Hong Chen¹ , Kejun Li¹ , Zhuo-Luo Xu¹ , Rong-Fang Shen⁶ , Yutong He⁷ , Tingyu Mou¹ , Ting-Yue Luo¹ , Xiangnan Sun⁵ , Zhao-Kun Wu¹ , Li-Jing Wang⁸ , Hong-Juan Liu² , Xiaozhong Qiu⁷ , Yi Gao⁹ , Xiaochun Bai¹⁰ , Wei Wang³ , Dalei Wu⁵ , Guoxin Li¹ , Wei-Jie Zhou^{1,2,3,4,9,11,*}

¹State Key Laboratory of Multi-organ Injury Prevention and Treatment, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
²Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China
³Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
⁴Department of Gastrointestinal and hernia surgery, Ganzhou Hospital-Nanfang Hospital, Southern Medical University, Ganzhou, Jiangxi, China
⁵State Key Laboratory of Microbial Technology, Shandong University, Qingdao, Shandong, China
⁶State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
⁷The Fifth Affiliated Hospital of Southern Medical University, Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Southern Medical University, Guangzhou, Guangdong, China
⁸Vascular Biology Research Institute, School of Life Sciences and Biopharmaceuticals, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
⁹General Surgery Center, Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China
¹⁰State Key Laboratory of Multi-organ Injury Prevention and Treatment, Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China
¹¹Division of Nephrology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China
^†These authors contributed equally: Wen-Hui Ma, Wen-Yi Li, Tao Chen, Linqian Jing
Correspondence: Wei-Jie Zhou(weijiezhouum@163.com)

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) expression, major histocompatibility complex (MHC) class I antigen presentation, and T cell intratumoral infiltration, all of which eventually inhibit tumor progression and enhance the effects of programmed cell death 1 (PD1) blockade. Thus, we have identified a previously unknown APC/PTPN13/STAT1-dependent tumor immune-suppressive mechanism. The potent tumor-suppressing effect of combining anti-PD1 antibodies with APC11 peptides provides a compelling target and rationale for future development of anti-tumor drugs for patients with CRC.

https://doi.org/10.1038/s41422-025-01206-4

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