南方医科大学周伟杰小组近日取得一项新成果。经过不懈努力，他们的最新研究揭示了C端APC的11-氨基酸肽靶向PTPN13可预防结直肠癌的免疫逃逸。2026年1月5日出版的《细胞研究》杂志发表了这项成果。

该课题组报道APC缺失通过蛋白酪氨酸磷酸酶非受体13 （PTPN13）对信号转导和转录激活因子1 （STAT1）的去磷酸化导致CD8⁺ T细胞浸润和CRC免疫逃避的抑制，而不依赖于β-catenin。含有APC （APC11）最后11个C端氨基酸（aa）残基的肽直接与PTPN13结合，阻断PTPN13 - STAT1相互作用，促进STAT1磷酸化、干扰素调节因子-1 （IRF1）表达、主要组织相容性复合体（MHC）I类抗原呈递和T细胞瘤内浸润，最终抑制肿瘤进展，增强程序性细胞死亡1（PD1）阻断的作用。因此，该课题组已经确定了一种以前未知的APC/PTPN13/ stat1依赖性肿瘤免疫抑制机制。抗PD1抗体联合APC11肽的有效肿瘤抑制作用为未来开发用于结直肠癌患者的抗肿瘤药物提供了一个令人信服的靶点和理论基础。

据了解，结直肠癌（CRC）对免疫检查点阻断在很大程度上仍然是难治的，80%-90%的病例存在大肠腺瘤性息肉病（APC）突变。以前认为APC的缺失主要通过解除Wnt/β-catenin信号的调控来促进肿瘤进展。

附：英文原文

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

Author: Ma, Wen-Hui, Li, Wen-Yi, Chen, Tao, Jing, Linqian, Chen, Yue-Hong, Li, Kejun, Xu, Zhuo-Luo, Shen, Rong-Fang, He, Yutong, Mou, Tingyu, Luo, Ting-Yue, Sun, Xiangnan, Wu, Zhao-Kun, Wang, Li-Jing, Liu, Hong-Juan, Qiu, Xiaozhong, Gao, Yi, Bai, Xiaochun, Wang, Wei, Wu, Dalei, Li, Guoxin, Zhou, Wei-Jie

Issue&Volume: 2026-01-05

Abstract: 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.

DOI: 10.1038/s41422-025-01206-4

Source: https://www.nature.com/articles/s41422-025-01206-4