Luka de Vos-Hillebrand, Simon Fietz, Philip Hillebrand, Zsófi Kulcsár, Marie Yatou Diop, Sarah Hollick, Alexander Philippe Maas, Sebastian Strieth, Jennifer Landsberg, Dimo Dietrich
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We analyzed <i>CD52</i> mRNA expression data from tumor bulk tissues of <i>N</i> = 445 untreated melanoma patients from The Cancer Genome Atlas (TCGA) Research Network and of <i>N</i> = 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 <i>N</i> = 4645 cells from <i>N</i> = 19 melanoma tissues, and <i>N</i> = 15,457 cells from normal skin provided by <i>N</i> = 5 donors. Higher <i>CD52</i> mRNA expression was associated with favorable OS (hazard ratio (HR) = 0.820, [95% CI 0.734–0.916], <i>p</i> < .001) in non-ICB-treated melanoma and with PFS (HR = 0.875, [95% CI 0.775–0.989], <i>p</i> = .033) and DC (<i>p</i> = .005) in ICB-treated melanoma. <i>CD52</i> expression correlated significantly with distinct immune cell subsets and correlated negatively with immune checkpoint expression in T cells. Moreover, our results suggest <i>CD52</i> expression by a certain type of tissue-resident macrophages. <i>CD52</i> mRNA was expressed in a small subgroup (8%) of immune checkpoint coexpressing melanoma cells. <i>CD52</i> expression is associated with features of ICB response in melanoma. 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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 <i>CD52</i> mRNA expression data from tumor bulk tissues of <i>N</i> = 445 untreated melanoma patients from The Cancer Genome Atlas (TCGA) Research Network and of <i>N</i> = 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 <i>N</i> = 4645 cells from <i>N</i> = 19 melanoma tissues, and <i>N</i> = 15,457 cells from normal skin provided by <i>N</i> = 5 donors. 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引用次数: 0
摘要
免疫调节蛋白CD52减弱淋巴细胞功能,并与自身免疫性疾病,如多发性硬化症(MS)有关。CD52是多发性硬化症和慢性淋巴细胞白血病(CLL)的治疗靶点。其表达在CLL和乳腺癌中具有预后和预测价值。它在黑色素瘤中的意义尚不清楚。我们分析CD52 mRNA表达肿瘤体积的数据组织N = 445治疗黑色素瘤患者的癌症基因组图谱(TCGA)研究网络和N = 121黑色素瘤患者接受anti-PD-1免疫检查点封锁(ICB)对结果(总生存期(OS),疾病控制(DC)和无进展生存(PFS)),单细胞RNA-Seq数据从N = 19 N = 4645细胞的黑色素瘤组织,和N = 15457 N = 5捐助者提供的细胞从正常皮肤。较高的CD52 mRNA表达与良好的OS相关(风险比(HR) = 0.820, [95% CI 0.734-0.916], p
CD52 mRNA expression predicts prognosis and response to immune checkpoint blockade in melanoma
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.
期刊介绍:
Pigment Cell & Melanoma Researchpublishes manuscripts on all aspects of pigment cells including development, cell and molecular biology, genetics, diseases of pigment cells including melanoma. Papers that provide insights into the causes and progression of melanoma including the process of metastasis and invasion, proliferation, senescence, apoptosis or gene regulation are especially welcome, as are papers that use the melanocyte system to answer questions of general biological relevance. Papers that are purely descriptive or make only minor advances to our knowledge of pigment cells or melanoma in particular are not suitable for this journal. Keywords
Pigment Cell & Melanoma Research, cell biology, melatonin, biochemistry, chemistry, comparative biology, dermatology, developmental biology, genetics, hormones, intracellular signalling, melanoma, molecular biology, ocular and extracutaneous melanin, pharmacology, photobiology, physics, pigmentary disorders