Tnfsf10, also known as tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), is a pro-apoptotic cytokine of the TNF superfamily. It binds to death receptors 4 and/or 5 on tumor cells, triggering intracellular caspase reactions and apoptosis [2]. It is involved in multiple biological processes, such as programmed cell death, and has potential significance in immune-related diseases and cancer [1,2].

In a triple-transgenic mouse model of Alzheimer's disease (3xTg-AD), blocking Tnfsf10 with a neutralizing monoclonal antibody attenuated amyloid-β-induced neurotoxicity, improved cognitive parameters, and decreased the protein expression of Tnfsf10, amyloid-β, inflammatory mediators, and GFAP in the hippocampus [5]. In breast cancer, an enhancer variant (rs13074711) associated with breast cancer susceptibility in Black women regulated Tnfsf10 expression, and Tnfsf10 played a role in the regulation of antiviral immune responses in triple-negative breast cancer (TNBC), with its deficiency in breast tumors decreasing tumor-infiltrated CD4+ and CD8+ T cell quantities [4]. In liver cancer cells, Ent-3α-formylabieta-8(14),13(15)-dien-16,12β-olide (EFLDO) sensitized cells to Tnfsf10-induced apoptosis in a p53-dependent manner, upregulating pro-apoptotic proteins and downregulating anti-apoptotic proteins [3].

In conclusion, Tnfsf10 is mainly known for its role in apoptosis induction. Studies using mouse models, such as in Alzheimer's disease and breast cancer, have revealed its significance in disease-related processes. It also shows potential in cancer treatment, as demonstrated by its role in liver cancer cell apoptosis. These findings suggest that Tnfsf10 could be a potential therapeutic target for certain diseases.

References:

1. Pyzik, Aleksandra, Grywalska, Ewelina, Matyjaszek-Matuszek, Beata, Roliński, Jacek. 2015. Immune disorders in Hashimoto's thyroiditis: what do we know so far? In Journal of immunology research, 2015, 979167. doi:10.1155/2015/979167. https://pubmed.ncbi.nlm.nih.gov/26000316/

2. Dhillon, Sohita. . Aponermin: First Approval. In Drugs, 84, 459-466. doi:10.1007/s40265-024-02004-9. https://pubmed.ncbi.nlm.nih.gov/38441805/

3. Qu, Yanbo, Liao, Zhixin, Wang, Xinzhu, Zhang, Jing, Liu, Chao. 2019. EFLDO sensitizes liver cancer cells to TNFSF10‑induced apoptosis in a p53‑dependent manner. In Molecular medicine reports, 19, 3799-3806. doi:10.3892/mmr.2019.10046. https://pubmed.ncbi.nlm.nih.gov/30896802/

4. Han, Yoo Jane, Zhang, Jing, Hardeman, Ashley, Huo, Dezheng, Olopade, Olufunmilayo I. . An enhancer variant associated with breast cancer susceptibility in Black women regulates TNFSF10 expression and antitumor immunity in triple-negative breast cancer. In Human molecular genetics, 32, 139-150. doi:10.1093/hmg/ddac168. https://pubmed.ncbi.nlm.nih.gov/35930348/

5. Cantarella, Giuseppina, Di Benedetto, Giulia, Puzzo, Daniela, Palmeri, Agostino, Bernardini, Renato. 2014. Neutralization of TNFSF10 ameliorates functional outcome in a murine model of Alzheimer's disease. In Brain : a journal of neurology, 138, 203-16. doi:10.1093/brain/awu318. https://pubmed.ncbi.nlm.nih.gov/25472798/