在宫颈癌的固有免疫和适应性免疫中，入侵前沿具有至关重要的免疫作用。
Crucial immunological roles of the invasion front in innate and adaptive immunity in cervical cancer.
机构信息
Laboratory for Immunotherapy, RIKEN Center for Integrative Medical Science, Yokohama, Kanagawa, 230-0045, Japan.
Department of Obstetrics and Gynecology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, 236-0004, Japan.
出版信息
Br J Cancer. 2024 Dec;131(11):1762-1774. doi: 10.1038/s41416-024-02877-3. Epub 2024 Oct 29.
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 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 CD4Tregs 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.
背景
先天免疫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。尽管宫颈癌（CC）表现出高复发率，但尚未分析其与肿瘤组织中淋巴细胞的关系。
方法
我们通过组织学分析，分析了 23 名接受治疗前的 CC 患者的外周血（PB）和肿瘤组织中的 NKT、NK 和 T 细胞。评估了它们之间在 PB 和肿瘤组织中的相关性。
结果
我们在 PB 中检测到功能性 NKT 和 NKG2D NK 细胞和效应 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 耗竭 CD8 T 细胞高度相关。我们确定了 PB 中 CD4Tregs 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。
Zotero 插件