研究动态
Articles below are published ahead of final publication in an issue. Please cite articles in the following format: authors, (year), title, journal, DOI.

卵巢癌的综合免疫转录组分析确定了一种以四种趋化因子为主的亚型,具有抗肿瘤免疫活性表型和良好的预后。

Integrated immuno-transcriptomic analysis of ovarian cancer identifies a four-chemokine-dominated subtype with antitumor immune-active phenotype and favorable prognosis.

发表日期:2024 Aug 02
作者: Lili Zhuo, Fanling Meng, Kaidi Sun, Meng Zhou, Jie Sun
来源: BRITISH JOURNAL OF CANCER

摘要:

卵巢癌(OV)是一种异质性疾病,但传统上被视为一种免疫冷恶性肿瘤。以 T 辅助细胞 1 (Th-1) 免疫反应为代表的免疫活性癌症表型与 OV 临床结果之间的关系仍不确定。我们编制了来自 19 个单独数据集的 2850 个 OV 样本的队列规模转录组数据概要,用于综合分析免疫转录组分析。排斥的免疫学常数被用作评估 Th-1/细胞毒性反应方向的指标,并研究免疫极化对 Th-1 免疫反应的临床生物学意义。我们分析了 39 个 OV 样本的单细胞 RNA 测序数据,以阐明免疫微环境的变异性,并对哈尔滨医科大学肿瘤医院的 39 个样本进行了免疫组织化学验证。我们的结果证明了 Th-1/细胞毒性的预后意义使用 OV 样本排斥分类的免疫学常数来分析肿瘤微环境 (TME) 内的免疫特征。具体来说,表达高水平 ICR 标记物的肿瘤患者的生存率显着提高。由四种趋化因子(CXCL9、CXCL10、CXCL11 和 CXCL13)组成的基因组被确定为介导活性 T 细胞炎症抗肿瘤表型建立的关键参与者。这种 4 趋化因子特征通过转录组学分析在外部多中心队列中得到了广泛验证,并通过免疫组织化学在独立的内部队列中得到了广泛验证,在 OV 中引入了一种新的免疫分类,并鉴定了与活性抗肿瘤免疫表型相关的趋化因子主导的亚型和预后良好。单细胞转录组分析表明,趋化因子主导的肿瘤主要通过巨噬细胞衍生的 CXCL9/10/11 的过表达来增加 CXCR3  NK 和 T 细胞向 TME 的募集。这项研究为理解 TME 内的免疫异质性提供了新的见解,并为进一步研究 TME 铺平了道路。为具有不同免疫特征的患者制定适当的治疗干预措施的方法。© 2024。作者,获得 Springer Nature Limited 的独家许可。
Ovarian cancer (OV) is a heterogeneous disease but has traditionally been treated as an immunologically cold malignancy. The relationship between the immune-active cancer phenotype typified by a T helper 1 (Th-1) immune response and clinical outcome in OV remains uncertain.A cohort-scale compendium of transcriptomic data from 2850 OV samples from 19 individual datasets was compiled for integrative immuno-transcriptomic analysis. The immunological constant of rejection was used as a metric to assess the Th-1/cytotoxic response orientation and investigate the clinical-biological significance of immune polarization towards a Th-1 immune response. Single-cell RNA sequencing data from 39 OV samples were analyzed to elucidate the variability of the immune microenvironment, and immunohistochemical validation was performed on 39 samples from the Harbin Medical University Cancer Hospital.Our results demonstrated the prognostic significance of a Th-1/cytotoxic immune profile within the tumor microenvironment (TME) using the immunological constant of rejection classification to OV samples. Specifically, patients with tumors expressing high levels of ICR markers showed significantly improved survival. A gene panel consisting of four chemokines (CXCL9, CXCL10, CXCL11 and CXCL13) was identified as critical players in mediating the establishment of an active T-cell-inflamed antitumor phenotype. This 4-chemokine signature, which was extensively validated in external multicenter cohorts through transcriptomic profiling and in an independent in-house cohort through immunohistochemistry, introduced a novel immune classification in OV and identified a chemokine-dominated subtype associated with an active antitumor immune phenotype and favorable prognosis. Single-cell transcriptomic analysis revealed that chemokine-dominated tumors increase CXCR3 + NK and T cell recruitment to the TME primarily through the overexpression of macrophage-derived CXCL9/10/11.This study provides new insights into understanding immune heterogeneity within the TME and paves the way for tailoring appropriate therapeutic interventions for patients with differing immune profiles.© 2024. The Author(s), under exclusive licence to Springer Nature Limited.