Tnfrsf1a, also known as TNFRSF1A (formerly TNFR1), encodes the 55 kDa TNF receptor. It is involved in inflammatory processes and is crucial for the regulation of the immune response, as TNF-α binding to this receptor activates various downstream signaling pathways [1].

Mutations in TNFRSF1A can cause TNF-receptor-associated periodic syndrome (TRAPS), presenting with prolonged fever and severe localized inflammation. These mutations often affect the first two cysteine-rich extracellular subdomains of the receptor, potentially impairing the cleavage of the TNFRSF1A ectodomain upon cellular activation, reducing the shedding of the soluble receptor which may act as an antagonist [1]. In multiple myeloma, TNFRSF1A overexpression leads to carfilzomib resistance by suppressing the expression of MHC genes and cell adhesion molecules, dampening antitumor immunity, while its silencing reverses resistance [2]. In osteosarcoma, TNFRSF1A was screened as a prognostic signature from necroptosis-related genes, with lower expression associated with a worse prognosis and changes in immune cell infiltration [3].

In conclusion, Tnfrsf1a is essential for normal immune-inflammatory regulation. Its mutations are linked to autoinflammatory syndromes like TRAPS. In cancer, it plays a role in drug resistance and prognosis, highlighting its importance in understanding disease mechanisms. Studies on Tnfrsf1a contribute to the understanding of immune-mediated diseases and cancer-related processes. [1,2,3]

References:

1. Galon, J, Aksentijevich, I, McDermott, M F, O'Shea, J J, Kastner, D L. . TNFRSF1A mutations and autoinflammatory syndromes. In Current opinion in immunology, 12, 479-86. doi:. https://pubmed.ncbi.nlm.nih.gov/10899034/

2. Zhao, Jie, Yang, Xuantao, Zhang, Haixi, Gu, Xuezhong. 2023. Identification of TNFRSF1A as a novel regulator of carfilzomib resistance in multiple myeloma. In Oncology research, 32, 325-337. doi:10.32604/or.2023.030770. https://pubmed.ncbi.nlm.nih.gov/38186567/

3. Zhang, Yuke, Liu, Kai, Wang, Jianzhong. . Identification of TNFRSF1A as a potential biomarker for osteosarcoma. In Cancer biomarkers : section A of Disease markers, 39, 299-312. doi:10.3233/CBM-230086. https://pubmed.ncbi.nlm.nih.gov/38250759/