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单细胞转录组学揭示了早发性与晚发性宫颈癌中多方面的免疫异质性。

Single-cell transcriptomics unveils multifaceted immune heterogeneity in early-onset versus late-onset cervical cancer.

作者信息

Chen Qian, Deng Dongfeng, Zhu Hong, Li Shan

机构信息

Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, China.

National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.

出版信息

World J Surg Oncol. 2025 Jan 14;23(1):12. doi: 10.1186/s12957-025-03654-z.

DOI:10.1186/s12957-025-03654-z
PMID:39810181
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11730844/
Abstract

Early-onset (EOCC) and late-onset cervical cancers (LOCC) represent two clinically distinct subtypes, each defined by unique clinical manifestations and therapeutic responses. However, their immunological profiles remain poorly explored. Herein, we analyzed single-cell transcriptomic data from 4 EOCC and 4 LOCC samples to compare their immune architectures. Epithelial cells in EOCC exhibited a notable dual immunological phenotype, characterized by immune-suppressive properties driven by elevated CXCL production, alongside immune-stimulatory features linked to heightened HLA molecule expression. CD4 + and CD8 + T cells in LOCC demonstrated a heightened activation state, while NK cells exhibited diminished cytotoxicity. Macrophages in LOCC displayed enhanced polarization towards both M1 and M2 phenotypes, along with dendritic cells showing augmented antigen-presenting capacity. Regarding cancer-associated fibroblasts (CAFs), EOCC was enriched with inflammatory CAFs, whereas LOCC harbored a higher proportion of antigen-presenting CAFs. These findings reveal the multifaceted immune heterogeneity between EOCC and LOCC, underscoring the imperative for age-tailored immunotherapeutic strategies.

摘要

早发性宫颈癌(EOCC)和晚发性宫颈癌(LOCC)是两种临床特征不同的亚型,每种亚型都有独特的临床表现和治疗反应。然而,它们的免疫特征仍未得到充分研究。在此,我们分析了4例EOCC和4例LOCC样本的单细胞转录组数据,以比较它们的免疫结构。EOCC中的上皮细胞表现出显著的双重免疫表型,其特征是由CXCL产生增加驱动的免疫抑制特性,以及与HLA分子表达升高相关的免疫刺激特征。LOCC中的CD4 +和CD8 + T细胞表现出更高的激活状态,而NK细胞的细胞毒性则降低。LOCC中的巨噬细胞对M1和M2表型的极化增强,同时树突状细胞的抗原呈递能力增强。关于癌症相关成纤维细胞(CAF),EOCC富含炎性CAF,而LOCC中抗原呈递CAF的比例更高。这些发现揭示了EOCC和LOCC之间多方面的免疫异质性,强调了制定针对年龄的免疫治疗策略的必要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/880c/11730844/82ac0dafad8b/12957_2025_3654_Fig7_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/880c/11730844/82ac0dafad8b/12957_2025_3654_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/880c/11730844/b2edfc978cae/12957_2025_3654_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/880c/11730844/5adea6d7f433/12957_2025_3654_Fig2_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/880c/11730844/589a07c6c13a/12957_2025_3654_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/880c/11730844/b6981d682e9d/12957_2025_3654_Fig6_HTML.jpg
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