Zhang Gengpu, Li Shengnan, Xiao Wanyi, Zhang Chao, Li Ting, Liao Zhichao, Liu Haotian, Xing Ruwei, Yao Wei, Yang Jilong
Department of Bone and Soft Tissue Tumor, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China.
Department of Oncology, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai 519000, China.
Cancers (Basel). 2024 Feb 23;16(5):908. doi: 10.3390/cancers16050908.
Immunotherapy is an essential therapy for individuals with advanced melanoma. However, not all patients respond to such treatment due to individual differences. We conducted a multidimensional analysis using transcriptome data from our center, as well as publicly available databases. We found that effective nivolumab treatment led to an upregulation of C2 levels, and higher levels following treatment are indicative of a good outcome. Through bioinformatics analyses and immunofluorescence, we identified a correlation between C2 and M1 macrophages. To further investigate the role of C2 in melanoma, we constructed subcutaneous tumorigenic models in C57BL/6 mice. The tumors in the C2 overexpression group exhibited significantly smaller sizes. Flow cytometric analysis of the mouse tumors demonstrated enhanced recruitment of macrophages, particularly of the M1 subtype, in the overexpression group. Moreover, single-cell RNA sequencing analysis revealed that C2-positive tumor cells exhibited enhanced communication with immune cells. We co-cultured tumor cell supernatants with macrophages in vitro and observed the induction of M1 subtype polarization. In addition, we discovered a close correlation between C2 and tertiary lymphoid structures. C2 has been demonstrated to exert a protective effect, mediated by its ability to modulate the tumor microenvironment. C2 serves as a prognostic marker for melanoma and can be employed to monitor the efficacy of immunotherapy.
免疫疗法是晚期黑色素瘤患者的重要治疗方法。然而，由于个体差异，并非所有患者都对这种治疗有反应。我们使用来自我们中心的转录组数据以及公开可用的数据库进行了多维分析。我们发现有效的纳武单抗治疗导致C2水平上调，治疗后较高的水平表明预后良好。通过生物信息学分析和免疫荧光，我们确定了C2与M1巨噬细胞之间的相关性。为了进一步研究C2在黑色素瘤中的作用，我们在C57BL/6小鼠中构建了皮下致瘤模型。C2过表达组的肿瘤尺寸明显较小。对小鼠肿瘤的流式细胞术分析表明，过表达组中巨噬细胞的募集增加，尤其是M1亚型。此外，单细胞RNA测序分析显示，C2阳性肿瘤细胞与免疫细胞的通讯增强。我们在体外将肿瘤细胞上清液与巨噬细胞共培养，并观察到M1亚型极化的诱导。此外，我们发现C2与三级淋巴结构之间存在密切相关性。已证明C2通过调节肿瘤微环境的能力发挥保护作用。C2可作为黑色素瘤的预后标志物，并可用于监测免疫治疗的疗效。
