Department of Dermatology and Venereology, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830000, China.
J Immunol Res. 2021 Feb 1;2021:6652846. doi: 10.1155/2021/6652846. eCollection 2021.
Basal cell carcinoma (BCC) is the most common skin cancer. While most of the basal cell carcinomas were localized lesion and can be easily managed, the treatment options to the advanced basal cell carcinomas are still remarkably limited. In recent years, proBDNF and its receptor p75NTR have been reported to play important roles in various diseases, including cancers and psychotic disorders. However, the role of p75NTR/proBDNF signaling in basal cell carcinoma remains unclear. Here, we found that the expression level of p75NTR/proBDNF was decreased in basal cell carcinoma patient samples and cell lines. In vitro study showed overexpression of p75NTR/proBDNF could significantly facilitate tumor cell death, including inflammatory-silent apoptosis and lytic inflammatory activated necroptosis. In vivo study showed overexpression of p75NTR/proBDNF dramatically promotes tumor-associated macrophage (M1) and T cell recruitment in a syngeneic mouse model of BCC. These results show a crucial role for p75NTR/proBDNF signaling in basal cell carcinoma immune microenvironment.
基底细胞癌（BCC）是最常见的皮肤癌。虽然大多数基底细胞癌是局限性病变，很容易治疗，但晚期基底细胞癌的治疗选择仍然非常有限。近年来，proBDNF 及其受体 p75NTR 已被报道在包括癌症和精神障碍在内的各种疾病中发挥重要作用。然而，p75NTR/proBDNF 信号在基底细胞癌中的作用尚不清楚。在这里，我们发现 p75NTR/proBDNF 的表达水平在基底细胞癌患者样本和细胞系中降低。体外研究表明，p75NTR/proBDNF 的过表达可显著促进肿瘤细胞死亡，包括炎症沉默型细胞凋亡和裂解炎症激活的坏死性凋亡。体内研究表明，p75NTR/proBDNF 的过表达在 BCC 的同基因小鼠模型中显著促进肿瘤相关巨噬细胞（M1）和 T 细胞的募集。这些结果表明 p75NTR/proBDNF 信号在基底细胞癌免疫微环境中起着至关重要的作用。
