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.

中文翻译：

---

p75NTR/proBDNF 通过坏死性凋亡信号通路调节基底细胞癌 (BCC) 免疫微环境

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部病变并且易于治疗，但晚期基底细胞癌的治疗选择仍然非常有限。近年来，据报道 proBDNF 及其受体 p75NTR 在各种疾病中发挥重要作用，包括癌症和精神病。然而，p75NTR/proBDNF 信号在基底细胞癌中的作用仍不清楚。在这里，我们发现基底细胞癌患者样本和细胞系中 p75NTR/proBDNF 的表达水平降低。体外研究表明，p75NTR/proBDNF 的过表达可以显着促进肿瘤细胞死亡，包括炎症沉默细胞凋亡和溶解性炎症激活的坏死性凋亡。体内研究表明 p75NTR/proBDNF 的过表达显着促进了 BCC 同源小鼠模型中肿瘤相关巨噬细胞 (M1) 和 T 细胞的募集。这些结果显示了 p75NTR/proBDNF 信号在基底细胞癌免疫微环境中的关键作用。