[1]钟守平,胡艳正.食管鳞状细胞癌组织中组织定居记忆T细胞分布浸润特征及与免疫治疗预后的关系研究[J].现代检验医学杂志,2025,40(02):11-16.[doi:10.3969/j.issn.1671-7414.2025.02.003]
　ZHONG Shouping,HU Yanzheng.Study on the Distribution and Infiltration Characteristics of Tissue Resident Memory T Cells in Esophageal Squamous Cell Carcinoma and Its Relationship with Immunotherapy Prognosis[J].Journal of Modern Laboratory Medicine,2025,40(02):11-16.[doi:10.3969/j.issn.1671-7414.2025.02.003]
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食管鳞状细胞癌组织中组织定居记忆T细胞分布浸润特征及与免疫治疗预后的关系研究()
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《现代检验医学杂志》[ISSN:/CN:]

卷:
第40卷
期数:
2025年02期
页码:
11-16
栏目:
论著
出版日期:
2025-03-15

文章信息/Info

Title:
Study on the Distribution and Infiltration Characteristics of Tissue Resident Memory T Cells in Esophageal Squamous Cell Carcinoma and Its Relationship with Immunotherapy Prognosis
文章编号:
1671-7414（2025）02-011-06
作者:
钟守平1; 胡艳正2
（1. 西安市中心医院心胸外科，西安710003；2. 咸阳市第一人民医院胸外科，陕西咸阳712000）
Author(s):
ZHONG Shouping1;  HU Yanzheng2
（1. Department of Cardiothoracic Surgery, Xi’an Central Hospital, Xi’an 710003，China；2. Department of Thoracic Surgery，the First People’s Hospital of Xianyang City， Shaanxi Xianyang 712000，China）
关键词:
食管鳞状细胞癌; 肿瘤浸润淋巴细胞; 组织定居记忆T 细胞; 免疫治疗
分类号:
R735.1；R730.43
DOI:
10.3969/j.issn.1671-7414.2025.02.003
文献标志码:
A
摘要:
目的 探究食管鳞状细胞癌（ESCC）组织中组织定居记忆T 细胞（TRM）的分布浸润特征，进一步分析TRM细胞浸润与ESCC 免疫治疗及预后的关系。方法 选取2017 年1 月～ 2019 年12 月西安市中心医院收治的术前未行新辅助治疗的30 例ESCC 患者癌灶组织和癌旁组织样本及外周静脉血样本；采用免疫荧光染色和流式细胞术检测各样本中CD103+CD8+TRM 细胞分布、表达浸润及免疫检查点分子[ 程序性死亡蛋白1（PD-1）和T 细胞免疫球蛋白和黏蛋白结构3（Tim-3）] 表达情况。另选取同期术前接受新辅助免疫检查点PD-1 抑制剂治疗的86 例ESCC 患者，取术后组织标本检测CD103+CD8+TRM 细胞浸润水平，分析其与免疫治疗疗效及预后的关系。结果 术前未行新辅助治疗的30 例ESCC 患者样本结果发现：① CD103 主要定位于肿瘤浸润性CD8+T 淋巴细胞的细胞膜；ESCC 癌灶组织中CD103+ 细胞大多共表达CD8+ 细胞，癌旁组织中CD103+ 细胞大多数则不共表达CD8+ 细胞。② ESCC 癌灶组织中CD103+CD8+TRM 细胞占CD8+T细胞的比例为76.9%±4.4%，明显高于癌旁正常组织的65.8%±3.6%，差异具有统计学意义（t=18.107，P ＜ 0.001）。③ESCC肿瘤浸润淋巴细胞中CD103+CD8+TRM细胞浸润比例为64.8%±4.3%，明显高于癌旁浸润淋巴细胞（34.6%±3.4%），差异具有统计学意义（t=30.175，P ＜ 0.001）；外周血淋巴细胞中几乎不表达。④ ESCC 癌灶组织CD103+CD8+TRM 细胞中免疫检查点分子PD-1 和Tim-3 高表达。术前接受新辅助免疫检查点PD-1 抑制剂治疗的86 例ESCC 患者样本结果发现：①免疫治疗有效组CD103+CD8+TRM 细胞浸润比例为76.5%±7.3%，明显高于免疫治疗无效组的58.7%±5.8%，差异具有统计学意义（t=12.126，P ＜ 0.001）。② CD103+CD8+TRM 细胞高浸润组较低浸润组具有更高的累积总生存率，差异具有统计学意义（Log-Rank χ2=2.635，P<0.05）。结论 ESCC 组织中CD103+CD8+TRM 细胞表达及浸润高于癌旁组织，其高浸润患者具有更好的免疫治疗疗效及预后生存，可作为新的生物学指标为临床预测ESCC 免疫治疗疗效及预后提供新的参考。
Abstract:
Objective To investigate the distribution and infiltration characteristics of tissue-resident memory (TRM) cells in esophageal squamous cell carcinoma (ESCC)，and further analyze relationship between TRM cell infiltration and ESCC immunotherapy and prognosis. Methods From January 2017 to December 2019, 30 ESCC patients who did not receive preoperative neoadjuvant therapy in Xi’an Central Hospital were selected as focal tissue and para cancer tissue samples and peripheral venous blood samples. Immunofluorescence staining and flow cytometry were used to detect the distribution, expression infiltration of CD103+CD8+TRM cells and the expression of immune checkpoint molecules [Programmed death- 1(PD-1) and T cell immunoglobulin and mucin domain 3 (Tim-3) ] in all samples. Another 86 ESCC patients who received neoadjuvant immune checkpoint PD-1 inhibitor treatment before surgery were selected during the same period, and the postoperative tissue samples were taken to detect the level of CD103+CD8+TRM cell infiltration, and the relationship between it and immunotherapy efficacy and prognosis was analyzed. Results The results of 30 ESCC patients who did not receive neoadjuvant therapy before surgery showed that: ① CD103 was mainly localized in the cell membrane of tumor-infiltrating CD8+T lymphocytes. Most of the CD103+ cells in ESCC cancer focus tissue co-express CD8+ cells, while most of the CD103+ cells in paracancer tissue did not co-express CD8+ cells. ② The proportion of CD103+CD8+TRM cells to CD8+T cells in ESCC cancer focus tissues was 76.9%±4.4%, which was significantly higher than that in adjacent normal tissues 65.8%±3.6%, and the difference was statistically significant(t=18.107, P ＜ 0.001). ③ The proportion of CD103+CD8+TRM cells in ESCC tumorinfiltrating lymphocytes was 64.8%±4.3%, which was significantly higher than that in para-carcinoma infiltrating lymphocytes 34.6%±3.4%, the difference was statistically significant(t=30.175, P ＜ 0.001), and peripheral blood lymphocytes were almost not expressed (1.1%±0.2%). ④The immune checkpoint molecules PD-1 and Tim-3 were highly expressed in CD103+CD8+TRM cells of ESCC cancer foci. A sample of 86 ESCC patients treated with neoadjuvant immune checkpoint PD-1 inhibitors before surgery found that: ① The proportion of CD103+CD8+TRM cell infiltration in the immunotherapy effective group was 76.5%±7.3%, which was significantly higher than that in immunotherapy ineffective group 58.7%±5.8%, the difference was statistically significant (t=12.126，P ＜ 0.001). ② The high infiltration group of CD103+CD8+TRM cells had higher OS survival than the low infiltration group, and the difference was statistically significant (Log-Rank χ2=2.635，P<0.05). Conclusion The expression and infiltration of CD103+CD8+TRM cells in ESCC tissues were higher than those in adjacent tissues, and the patients with high infiltration had better immunotherapy efficacy and survival prognosis, which could be used as a new biological indicator to provide a new reference for clinical prediction of the efficacy and prognosis of ESCC immunotherapy.

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备注/Memo

备注/Memo:
基金项目：陕西省自然科学基础研究计划项目（2020JQ-308）。
作者简介：钟守平（1974-），男，本科，副主任医师，研究方向：心胸外科，E-mail：fit_02213@163.com。
通讯作者：胡艳正（1986-），男，硕士研究生，副主任医师，研究方向: 肺癌、食管癌、纵隔肿瘤、胸部外伤，E-mail：foxyanzheng@126.com。
更新日期/Last Update: 2025-03-15