Tap1-KO Mouse

Tap1, also known as transporter associated with antigen processing 1, is a member of the ATP-binding cassette (ABC) family. It is crucial for transporting antigen peptides from the cytoplasm to the lumen of the endoplasmic reticulum, which are then loaded onto major histocompatibility complex (MHC) class I molecules. This process is essential for antigen presentation and the regulation of adaptive immunity. Additionally, Tap1 is an interferon-stimulated gene product that can activate the TBK1-IRF3-mediated type I interferon production, showing broadly antiviral activities [9].

Tap1 has been associated with various diseases. In ankylosing spondylitis, certain polymorphisms in Tap1 (Tap1-333Val, Tap1-637Gly) are likely to be associated with the disease, especially when compared with HLA-B27-negative controls [1]. In uveal melanoma, upregulated Tap1 is associated with shorter survival time, higher metastasis likelihood, and higher mortality. In vitro silencing of Tap1 in C918 cells inhibited cell proliferation and metastasis [2]. In gastric cancer, Tap1 was identified as a T-cell related therapeutic target, and oxaliplatin can enhance immunotherapy by promoting Tap1 expression [3]. In pancreatic cancers, Tap1 promotes resistance to MEK inhibitors, and its suppression can sensitize resistant cells [4]. In colorectal cancer, down-regulation of Tap1 is a mechanism of tumor immune escape and a poor prognostic factor [5]. In gastric carcinoma, Tap1 is linked to an inflamed tumor microenvironment and can be a biomarker for immunotherapeutic responses [6]. Across multiple cancer types, Tap1 expression has prognostic value and is correlated with immune-related pathways and immunotherapeutic biomarkers [7]. In locally advanced gastric cancer, high Tap1 expression is associated with better overall survival [8].

In conclusion, Tap1 plays a vital role in antigen presentation, antiviral defense, and is involved in the pathogenesis and prognosis of multiple diseases, especially various cancers. Research on Tap1, including through genetic models, has provided insights into its functions in these biological processes and disease conditions, potentially guiding new therapeutic strategies.

References:

1. Qian, Yufeng, Wang, Genlin, Xue, Feng, Tang, Liang, Yang, Huilin. 2017. Genetic association between TAP1 and TAP2 polymorphisms and ankylosing spondylitis: a systematic review and meta-analysis. In Inflammation research : official journal of the European Histamine Research Society ... [et al.], 66, 653-661. doi:10.1007/s00011-017-1047-1. https://pubmed.ncbi.nlm.nih.gov/28405734/

2. Zhu, Ru, Chen, Yu-Ting, Wang, Bo-Wen, Jiang, Fa-Gang, Zhang, Ming-Chang. 2023. TAP1, a potential immune-related prognosis biomarker with functional significance in uveal melanoma. In BMC cancer, 23, 146. doi:10.1186/s12885-023-10527-9. https://pubmed.ncbi.nlm.nih.gov/36774490/

3. Zhao, Yupeng, Liu, Ziyuan, Deng, Kaiyuan, Li, Ranran, Xia, Jiazeng. 2024. Identification of TAP1 as a T-cell related therapeutic target in gastric cancer by mediating oxalipliatin-related synergistic enhancement of immunotherapy. In International immunopharmacology, 132, 111998. doi:10.1016/j.intimp.2024.111998. https://pubmed.ncbi.nlm.nih.gov/38593510/

4. Li, Boya, Feng, Yu, Hou, Qiaoyun, Fu, Yan, Luo, Yongzhang. 2022. Antigen Peptide Transporter 1 (TAP1) Promotes Resistance to MEK Inhibitors in Pancreatic Cancers. In International journal of molecular sciences, 23, . doi:10.3390/ijms23137168. https://pubmed.ncbi.nlm.nih.gov/35806187/

5. Ling, Agnes, Löfgren-Burström, Anna, Larsson, Pär, Edin, Sofia, Palmqvist, Richard. 2017. TAP1 down-regulation elicits immune escape and poor prognosis in colorectal cancer. In Oncoimmunology, 6, e1356143. doi:10.1080/2162402X.2017.1356143. https://pubmed.ncbi.nlm.nih.gov/29147604/

6. He, Zehua, Yang, Hong, Chen, Qingfeng, He, Wanrong, Chen, Zhihui. 2024. Role of TAP1 in the identification of immune-hot tumor microenvironment and its prognostic significance for immunotherapeutic efficacy in gastric carcinoma. In Journal of gastrointestinal oncology, 15, 890-907. doi:10.21037/jgo-24-28. https://pubmed.ncbi.nlm.nih.gov/38989426/

7. Tu, Zewei, Li, Kuangxun, Ji, Qiankun, Huang, Kai, Zhu, Xingen. 2023. Pan-cancer analysis: predictive role of TAP1 in cancer prognosis and response to immunotherapy. In BMC cancer, 23, 133. doi:10.1186/s12885-022-10491-w. https://pubmed.ncbi.nlm.nih.gov/36759763/

8. Segami, Kenki, Aoyama, Toru, Hiroshima, Yukihiko, Saeki, Hiroshi, Oshima, Takashi. . Clinical Significance of TAP1 and DLL4 Expression in Patients With Locally Advanced Gastric Cancer. In In vivo (Athens, Greece), 35, 2771-2777. doi:10.21873/invivo.12562. https://pubmed.ncbi.nlm.nih.gov/34410967/

9. Zhao, Jin, Li, Ruiting, Li, Yanjun, Feng, Fengling, Sun, Caijun. 2021. Broadly Antiviral Activities of TAP1 through Activating the TBK1-IRF3-Mediated Type I Interferon Production. In International journal of molecular sciences, 22, . doi:10.3390/ijms22094668. https://pubmed.ncbi.nlm.nih.gov/33925089/