Department of Tumor and Immunology in Precision Medical Institute, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710000, P. R. China.
National and Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710000, China.
BMC Cancer. 2024 Nov 18;24(1):1419. doi: 10.1186/s12885-024-13191-9.
Many investigation have sought to identify therapeutic targets and treatment strategies for skin cutaneous melanoma (SKCM). Numb, an endocytic adaptor protein, is known to act as a tumor suppressor in various human cancers. However, the roles of Numb and its homolog NumbL in immune microenvironment, and their effect on melanoma remain largely unexplored.
We analyzed the expression levels of Numb and NumbL, as well as immune signatures of SKCM patients by UCSCXenaShiny v1 database. We also constructed animal model using Numb and NumbL conditional knockout (cKO) mice. Distribution analysis of immune cells in tumors was performed by flow cytometry and pathology staining.
Numb and NumbL were found to be consistently expressed at low levels in SKCM patients. In addition, alterations in tumor immune microenvironment were identified. The CD8 T, CD19 B, and NK1.1 CD49 cells were decreased in tumors of Numb and NumbL cKO mice, confirming previous bioinformatics analysis of immune signatures. Additionally, we observed CD68 macrophages to be increased as judged by tumor pathology staining.
Numb and NumbL were found to inhibit melanoma cell growth by modulating immune cell activity. These results suggested that Numb and NumbL may be potential therapeutic targets for SKCM patient immunotherapy.
许多研究试图确定皮肤黑色素瘤（SKCM）的治疗靶点和治疗策略。NUMB 是一种内吞衔接蛋白，已知在多种人类癌症中作为肿瘤抑制因子发挥作用。然而，NUMB 及其同源物 NUMBL 在免疫微环境中的作用及其对黑色素瘤的影响在很大程度上仍未被探索。
我们通过 UCSCXenaShiny v1 数据库分析了 SKCM 患者 NUMB 和 NUMBL 的表达水平以及免疫特征。我们还使用 NUMB 和 NUMBL 条件敲除（cKO）小鼠构建了动物模型。通过流式细胞术和病理染色分析肿瘤中免疫细胞的分布。
NUMB 和 NUMBL 在 SKCM 患者中均呈低水平一致表达。此外，还发现肿瘤免疫微环境发生改变。NUMB 和 NUMBL cKO 小鼠肿瘤中的 CD8T、CD19B 和 NK1.1 CD49 细胞减少，证实了之前对免疫特征的生物信息学分析。此外，我们通过肿瘤病理染色观察到 CD68 巨噬细胞增加。
NUMB 和 NUMBL 通过调节免疫细胞活性抑制黑色素瘤细胞生长。这些结果表明 NUMB 和 NUMBL 可能是 SKCM 患者免疫治疗的潜在治疗靶点。
