{"title":"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。","authors":"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","doi":"10.1038/s41416-024-02877-3","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>We detected functional NKT and NKG2D<sup>hi</sup> NK cells and effector CD4<sup>+</sup> Tregs in PB. In the tumor, we detected the infiltration of LAG-3<sup>+</sup> TIM-3<sup>+</sup> CD4<sup>+</sup> and CD8<sup>+</sup> 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<sup>+</sup> TIM-3<sup>+</sup> CD8<sup>+</sup> T cells are highly associated with CD69<sup>+</sup> CD103<sup>-</sup> exhausted CD8<sup>+</sup> T cells. We identified the statistical relationship between CD4<sup>+</sup>Tregs in PB and the number of LAG-3<sup>+</sup> TIM-3<sup>+</sup> CD4<sup>+</sup> T cells in the IF, which may be related to recurrence in patients with CC.</p><p><strong>Conclusions: </strong>LAG-3<sup>+</sup> TIM-3<sup>+</sup> T cells located in the IF may play a key role in regulation of the tumor immune microenvironment.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":6.4000,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Crucial immunological roles of the invasion front in innate and adaptive immunity in cervical cancer.\",\"authors\":\"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\",\"doi\":\"10.1038/s41416-024-02877-3\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>We detected functional NKT and NKG2D<sup>hi</sup> NK cells and effector CD4<sup>+</sup> Tregs in PB. In the tumor, we detected the infiltration of LAG-3<sup>+</sup> TIM-3<sup>+</sup> CD4<sup>+</sup> and CD8<sup>+</sup> 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<sup>+</sup> TIM-3<sup>+</sup> CD8<sup>+</sup> T cells are highly associated with CD69<sup>+</sup> CD103<sup>-</sup> exhausted CD8<sup>+</sup> T cells. We identified the statistical relationship between CD4<sup>+</sup>Tregs in PB and the number of LAG-3<sup>+</sup> TIM-3<sup>+</sup> CD4<sup>+</sup> T cells in the IF, which may be related to recurrence in patients with CC.</p><p><strong>Conclusions: </strong>LAG-3<sup>+</sup> TIM-3<sup>+</sup> T cells located in the IF may play a key role in regulation of the tumor immune microenvironment.</p>\",\"PeriodicalId\":9243,\"journal\":{\"name\":\"British Journal of Cancer\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":6.4000,\"publicationDate\":\"2024-10-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"British Journal of Cancer\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1038/s41416-024-02877-3\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"British Journal of Cancer","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41416-024-02877-3","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
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。
Crucial immunological roles of the invasion front in innate and adaptive immunity in cervical cancer.
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.
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.