Crucial immunological roles of the invasion front in innate and adaptive immunity in cervical cancer.

IF 6.4 1区医学 Q1 ONCOLOGY

British Journal of Cancer Pub Date : 2024-10-29 DOI:10.1038/s41416-024-02877-3

Yuhya Hirahara, Kanako Shimizu, Satoru Yamasaki, Tomonori Iyoda, Shogo Ueda, Shinya Sato, Jotaro Harada, Haruya Saji, Satoshi Fujii, Yohei Miyagi, Etsuko Miyagi, Shin-Ichiro Fujii

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引用次数: 0

Abstract

Background: The immunostimulatory actions of innate and adaptive immune responses play a crucial role in the cancer-immunity cycle. Although cervical cancer (CC) exhibits a high recurrence rate, the relation with lymphocytes in the tumor tissue have not been analyzed.

Methods: We analyzed NKT, NK, and T cells, not only in peripheral blood (PB), but also tumor tissue through histological analysis from 23 patients with CC collected before treatment. A correlation of them between PB and the tumor tissue were assessed.

Results: We detected functional NKT and NKG2D^hi NK cells and effector CD4⁺ Tregs in PB. In the tumor, we detected the infiltration of LAG-3⁺ TIM-3⁺ CD4⁺ and CD8⁺ T cells rather than NK cells particularly in the invasion front (IF) by fluorescent multiplex immunohistochemistry. The heatmap and correlation analysis revealed that LAG-3⁺ TIM-3⁺ CD8⁺ T cells are highly associated with CD69⁺ CD103^- exhausted CD8⁺ T cells. We identified the statistical relationship between CD4⁺Tregs in PB and the number of LAG-3⁺ TIM-3⁺ CD4⁺ T cells in the IF, which may be related to recurrence in patients with CC.

Conclusions: LAG-3⁺ TIM-3⁺ T cells located in the IF may play a key role in regulation of the tumor immune microenvironment.

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侵袭前沿在宫颈癌先天性免疫和适应性免疫中的关键免疫学作用。

背景：先天性免疫反应和适应性免疫反应的免疫刺激作用在癌症-免疫循环中起着至关重要的作用。虽然宫颈癌（CC）的复发率很高，但尚未分析其与肿瘤组织中淋巴细胞的关系：方法：我们不仅对外周血（PB）中的 NKT、NK 和 T 细胞进行了分析，还通过组织学分析对 23 名宫颈癌患者治疗前的肿瘤组织进行了分析。评估了外周血与肿瘤组织之间的相关性：结果：我们在PB中检测到了功能性NKT和NKG2Dhi NK细胞以及效应CD4+ Tregs。在肿瘤中，我们通过荧光多重免疫组化检测到 LAG-3+ TIM-3+ CD4+ 和 CD8+ T 细胞而非 NK 细胞的浸润，尤其是在侵袭前沿（IF）。热图和相关性分析表明，LAG-3+ TIM-3+ CD8+ T细胞与CD69+ CD103- 精疲力竭的CD8+ T细胞高度相关。我们确定了 PB 中 CD4+Tregs 与 IF 中 LAG-3+ TIM-3+ CD4+ T 细胞数量之间的统计学关系，这可能与 CC 患者的复发有关：结论：位于IF中的LAG-3+ TIM-3+ T细胞可能在调节肿瘤免疫微环境中发挥关键作用。

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

British Journal of Cancer 医学-肿瘤学

CiteScore

15.10

自引率

1.10%

发文量

383

审稿时长

6 months

期刊介绍： The British Journal of Cancer is one of the most-cited general cancer journals, publishing significant advances in translational and clinical cancer research.It also publishes high-quality reviews and thought-provoking comment on all aspects of cancer prevention,diagnosis and treatment.