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

IF 6.4 1区 医学 Q1 ONCOLOGY
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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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 NKG2Dhi 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.

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
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.
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