研究动态
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C-X-C基序趋化因子配体9与三阴性乳腺癌良好预后相关,通过促进免疫细胞浸润起作用。

C-X-C motif chemokine ligand 9 correlates with favorable prognosis in triple-negative breast cancer by promoting immune cell infiltration.

发表日期:2023 Sep 05
作者: Xi Cao, Yu Song, Huanwen Wu, Xinyu Ren, Qiang Sun, Zhiyong Liang
来源: Cell Death & Disease

摘要:

C-X-C motif chemokine ligand 9(CXCL9)通过招募、增殖和激活免疫细胞,在抗肿瘤免疫中发挥重要作用。本研究通过组织微阵列评估了268例三阴性乳腺癌(TNBC)患者中CXCL9和PD-L1的表达模式。分析了CXCL9在免疫细胞(ICs)或肿瘤细胞(TCs)中的表达与临床病理参数、PD-L1表达、肿瘤浸润淋巴细胞(TILs)以及生存状况之间的关系。此外,我们还分析了癌基因组图谱(TCGA)中包含139例TNBC患者的数据集,以明确CXCL9的表达与其他免疫基因表达、免疫浸润和预后之间的相关性。组织微阵列研究(n=268)的结果显示,80.6%的病例中表达了CXCL9,其中在ICs中的表达水平高于TCs(中位数:1% vs 0%)。CXCL9在≥1%的ICs中的表达被归类为CXCL9-IC阳性组。CXCL9-IC的表达与PD-L1表达、CD3+TILs、CD4+TILs、CD8+TILs和CD19+TILs均呈强烈正相关(所有P<0.0001)。生存分析显示,CXCL9-IC阳性组的无病生存期延长(P=0.038),总生存期延长(P=0.023)与阴性组相比。TCGA队列的分析结果(n=138)显示,CXCL9的升高表达与B细胞、巨噬细胞、自然杀伤细胞、单核细胞的浸润增加,免疫检查点分子和其他CXCL家族成员,包括CXCL10和CXCL11的表达增加相关。这些发现证实了CXCL9在抗肿瘤免疫中的调控作用,并提示其在涉及免疫检查点阻滞治疗中可能发挥潜在作用。
C-X-C motif chemokine ligand 9 (CXCL9) plays an important role in antitumor immunity through the recruitment, proliferation, and activation of immune cells. Here, we evaluated the expression patterns of CXCL9 and programmed death-ligand 1 (PD-L1) in a cohort of 268 patients with triple-negative breast cancer (TNBC) by tissue microarray. The correlations between CXCL9 expression in immune cells (ICs) or tumor cells (TCs) and clinicopathologic parameters, PD-L1 expression, tumor-infiltrating lymphocytes (TILs) and survival were analyzed in this cohort (n=268). Additionally, we analyzed a TNBC dataset (n=138) from The Cancer Genome Atlas (TCGA) to identify correlation between CXCL9 expression and other immune gene expression, immune infiltration, and prognosis. The results of the tissue microarray cohort (n=268) showed that CXCL9 was expressed in 80.6% cases, with elevated expression levels in ICs relative to in TCs (median: 1% vs 0%). CXCL9 expressed in ≥1% of ICs was categorized as the CXCL9-IC-positive group. CXCL9-IC expression was strongly and positively correlated with the PD-L1 expression, CD3+ TILs, CD4+ TILs, CD8+ TILs, and CD19+ TILs (all P<0.0001). Survival analyses showed that the CXCL9-IC-positive group demonstrated prolonged disease-free survival (P=0.038) and overall survival (P=0.023) compared with the negative group. The analyses from TCGA cohort (n=138) showed that elevated CXCL9 expression correlated with increased infiltration of B-cells, macrophages, natural killer cells, monocytes and increased expression of immune checkpoint molecules and other CXCL family members, including CXCL10 and CXCL11. These findings confirm the regulatory role of CXCL9 in antitumor immunity and suggest a potential role in treatments involving immune-checkpoint blockade.