The immune-modulating protein CD52 attenuates lymphocyte function and is associated with autoimmune disorders, for example, multiple sclerosis (MS). CD52 represents a therapeutic target in MS and chronic lymphocytic leukemia (CLL). Its expression has prognostic and predictive value in CLL and is prognostic in breast cancer. Its significance in melanoma is unclear. We analyzed CD52 mRNA expression data from tumor bulk tissues of N = 445 untreated melanoma patients from The Cancer Genome Atlas (TCGA) Research Network and of N = 121 melanoma patients undergoing anti-PD-1 immune checkpoint blockade (ICB) with regard to outcome (overall survival [OS], disease control [DC], and progression-free survival [PFS]), single-cell RNA-Seq data of N = 4645 cells from N = 19 melanoma tissues, and N = 15,457 cells from normal skin provided by N = 5 donors. Higher CD52 mRNA expression was associated with favorable OS (hazard ratio (HR) = 0.820, [95% CI 0.734–0.916], p < .001) in non-ICB-treated melanoma and with PFS (HR = 0.875, [95% CI 0.775–0.989], p = .033) and DC (p = .005) in ICB-treated melanoma. CD52 expression correlated significantly with distinct immune cell subsets and correlated negatively with immune checkpoint expression in T cells. Moreover, our results suggest CD52 expression by a certain type of tissue-resident macrophages. CD52 mRNA was expressed in a small subgroup (8%) of immune checkpoint coexpressing melanoma cells. CD52 expression is associated with features of ICB response in melanoma. Concomitant ICB and anti-CD52 treatment requires critical review.

中文翻译：

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CD52 mRNA 表达预测黑色素瘤的预后和对免疫检查点阻断的反应

免疫调节蛋白 CD52 会减弱淋巴细胞功能，并与自身免疫性疾病有关，例如多发性硬化症 (MS)。CD52 代表 MS 和慢性淋巴细胞白血病 (CLL) 的治疗靶点。其表达在 CLL 中具有预后和预测价值，并且在乳腺癌中具有预后价值。它在黑色素瘤中的意义尚不清楚。我们分析了来自癌症基因组图谱 (TCGA) 研究网络的N  = 445 名未经治疗的黑色素瘤患者和接受抗 PD-1 免疫检查点阻断 (ICB) 的N =  121 名黑色素瘤患者的肿瘤块组织的 CD52 mRNA 表达数据的结果（总生存期 [OS]、疾病控制 [DC] 和无进展生存期 [PFS]），来自N = 19 个黑色素瘤组织的N  = 4645 个细胞 和来自正常皮肤的N  = 15,457 个细胞的单细胞 RNA-Seq 数据由N = 5 个捐赠者提供 。 在非 ICB 治疗的黑色素瘤中，较高的CD52 mRNA 表达与良好的 OS（风险比 (HR) = 0.820，[95% CI 0.734–0.916]，p < .001）和 PFS 相关（HR = 0.875，[95%  ICB 治疗的黑色素瘤中的CI 0.775–0.989]，p  = .033) 和 DC ( p = .005)。CD52表达与不同的免疫细胞亚群显着相关，与 T 细胞中的免疫检查点表达呈负相关。此外，我们的结果表明CD52由某种类型的组织驻留巨噬细胞表达。CD52 mRNA 在共表达黑色素瘤细胞的免疫检查点小亚组 (8%) 中表达。CD52表达与黑色素瘤中 ICB 反应的特征相关。ICB 和抗 CD52 联合治疗需要严格审查。