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手段。然而，由于个体差异，并非所有患者均对该疗法产生应答。我们利用本中心的转录组数据及公共数据库进行了多维度分析，发现有效的纳武利尤单抗治疗可导致C2水平上调，且治疗后较高的C2水平提示良好预后。通过生物信息学分析与免疫荧光技术，我们确定了C2与M1型巨噬细胞之间的相关性。为深入探究C2在黑色素瘤中的作用，我们在C57BL/6小鼠中构建了皮下成瘤模型。C2过表达组的肿瘤体积显著缩小。对小鼠肿瘤的流式细胞分析显示，过表达组巨噬细胞（特别是M1亚型）的募集能力增强。单细胞RNA测序分析进一步揭示，C2阳性肿瘤细胞与免疫细胞的通讯作用增强。在体外实验中，我们将肿瘤细胞上清液与巨噬细胞共培养，观察到其可诱导M1亚型极化。此外，我们发现C2与三级淋巴结构存在密切关联。研究证实C2通过调节肿瘤微环境发挥保护作用，可作为黑色素瘤的预后标志物，并用于监测免疫治疗效果。
肿瘤(癌症)患者之家