AURKA Enhances Antitumor Immunity by Activating CD4+ T Cell Proliferation in Colorectal Cancer.

IF 1.9 4区医学 Q3 ONCOLOGY

Cancer Investigation Pub Date : 2025-09-25 DOI:10.1080/07357907.2025.2559403

Yidong Xu, Wei Wang, Jiazi Yu, Jianpei Zhao, Xiaoyu Dai, Zhongchen Liu

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引用次数: 0

Abstract

Introduction: Colorectal cancer (CRC) ranks third globally in cancer incidence. Aurora Kinase A (AURKA) critically regulates tumor proliferation and microenvironment, yet its dual CRC roles remain unclear.

Methods: We integrated bulk RNA-seq, scRNA-seq, and 10x Visium spatial transcriptomics to profile AURKA. Immune infiltration was assessed via CIBERSORT/ssGSEA. Clinical validation used IHC/HE staining. Immunotherapy associations were tested in ICB cohorts and murine models.

Results: Pan-cancer analysis showed CRC-specific AURKA prognostic value (p < 0.05). High AURKA correlated with prolonged OS (median 68 vs 42 months; log-rank P = 0.034), conventional adenocarcinoma (p < 0.001), left-sided tumors (p < 0.001), and absent perineural invasion (p = 0.041). Pathway analyses linked AURKA to cell cycle (G2/M checkpoint) and immune pathways (IL-2/STAT5). Spatial transcriptomics identified peritumoral niches (clusters 6/7/12) co-expressing AURKA, CD4, MKI67, and immune-activation markers (HLA-DRB1, CXCL10). IHC confirmed AURKA-CD4 + T-cell correlation (R = 0.66, p < 0.05). scRNA-seq revealed AURKA dominance in proliferating T cells. High AURKA predicted anti-PD-1 response (HR = 0.44, p = 0.003) and CD4+ memory T-cell expansion in murine models.

Conclusion: AURKA dually regulates tumor proliferation and immune engagement. Its spatial enrichment in T-cell niches supports its use as an immunotherapy biomarker.

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AURKA通过激活结直肠癌CD4+ T细胞增殖增强抗肿瘤免疫。

导读：结直肠癌（Colorectal cancer， CRC）在全球癌症发病率中排名第三。极光激酶A （Aurora Kinase A， AURKA）对肿瘤增殖和微环境有重要调控作用，但其在结直肠癌中的双重作用尚不清楚。方法：我们整合了bulk RNA-seq， scRNA-seq和10x Visium空间转录组学来分析AURKA。通过CIBERSORT/ssGSEA评估免疫浸润。临床验证采用免疫组化/HE染色。在ICB队列和小鼠模型中测试了免疫治疗的相关性。结果：泛癌分析显示crc特异性AURKA预后价值（p = 0.034），常规腺癌（p = 0.041）。通路分析将AURKA与细胞周期（G2/M检查点）和免疫通路（IL-2/STAT5）联系起来。空间转录组学鉴定了肿瘤周围生态位（6/7/12簇）共同表达AURKA、CD4、MKI67和免疫激活标志物（HLA-DRB1、CXCL10）。IHC证实AURKA-CD4 + t细胞相关性（R = 0.66, p p = 0.003）和小鼠模型中CD4+记忆t细胞扩增。结论：AURKA对肿瘤增殖和免疫参与具有双重调节作用。其在t细胞壁龛中的空间富集支持其作为免疫治疗生物标志物的使用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer Investigation 医学-肿瘤学

CiteScore

3.80

自引率

4.20%

发文量

审稿时长

8.5 months

期刊介绍： Cancer Investigation is one of the most highly regarded and recognized journals in the field of basic and clinical oncology. It is designed to give physicians a comprehensive resource on the current state of progress in the cancer field as well as a broad background of reliable information necessary for effective decision making. In addition to presenting original papers of fundamental significance, it also publishes reviews, essays, specialized presentations of controversies, considerations of new technologies and their applications to specific laboratory problems, discussions of public issues, miniseries on major topics, new and experimental drugs and therapies, and an innovative letters to the editor section. One of the unique features of the journal is its departmentalized editorial sections reporting on more than 30 subject categories covering the broad spectrum of specialized areas that together comprise the field of oncology. Edited by leading physicians and research scientists, these sections make Cancer Investigation the prime resource for clinicians seeking to make sense of the sometimes-overwhelming amount of information available throughout the field. In addition to its peer-reviewed clinical research, the journal also features translational studies that bridge the gap between the laboratory and the clinic.