新辅助化学免疫治疗后肺癌中肿瘤远端纵隔淋巴结含有肿瘤相关祖细胞耗竭 T 细胞
Tumor-distal mediastinal lymph nodes harbor tumor-related progenitor exhausted T cells in lung cancer after neoadjuvant chemoimmunotherapy.
作者
作者单位
- Department of Lung Cancer, Tianjin Lung Cancer Center, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China. Electronic address: zhangbin_09@tmu.edu.cn.
- Department of Lung Cancer, Tianjin Lung Cancer Center, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
- Department of Radiology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China.
- Department of Pathology, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
- Cancer Molecular Diagnostics Core, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China; Key Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, China; Key Laboratory of Cancer Immunology and Biotherapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, China.
- Department of Lung Cancer, Tianjin Lung Cancer Center, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China. Electronic address: wangchangli@tjmuch.com.
- Department of Lung Cancer, Tianjin Lung Cancer Center, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China. Electronic address: zhangzhenfa@tmu.edu.cn.
- Department of Lung Cancer, Tianjin Lung Cancer Center, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China. Electronic address: yuedongsheng@tmu.edu.cn.
摘要
中文
肿瘤近端纵隔淋巴结（tpMLNs）支持祖细胞耗竭 CD8+ T 细胞（CD8+ Tpex）介导的抗肿瘤免疫，但肿瘤远端纵隔淋巴结（tdMLNs）在肺鳞状细胞癌（LUSC）新辅助化学免疫治疗后的作用仍不清楚。对接受新辅助化学免疫治疗的五名 LUSC 患者中来自五个解剖部位的 28 个样本进行单细胞免疫表型分析，揭示 tpMLNs 和 tdMLNs 之间的免疫细胞组成相似。值得注意的是，肿瘤中的终末分化耗竭 CD8+ T 淋巴细胞（CD8+ Tex-term）与 tpMLNs 和 tdMLNs 中的 CD8+ Tpex 群体共享克隆谱系。多重免疫荧光分析确认 TOX+TCF-1+CXCL13+ CD8+ Tpex 存在于 tpMLNs 和 tdMLNs 中，但不存在于原发肿瘤中。术后 1、6 和 18 个月的克隆追踪检测到外周血中肿瘤来源的 CD8+ Tex-term 和 CD8+ Tpex 相关克隆。这些发现表明 tdMLNs 在 LUSC 抗肿瘤免疫反应中发挥类似 tpMLNs 的免疫功能。因此，我们建议在手术切除期间保留 tdMLNs，以维持这些免疫效应细胞储备，并支持术后免疫能力和辅助治疗结果。
English
Tumor-proximal mediastinal lymph nodes (tpMLNs) support progenitor exhausted CD8+ T cells (CD8+ Tpex)-mediated antitumor immunity, but the role of tumor-distal mediastinal lymph nodes (tdMLNs) in lung squamous cell carcinoma (LUSC) after neoadjuvant chemoimmunotherapy remains unclear. Single-cell immunophenotypic analysis of 28 samples from five anatomic sites in five LUSC patients receiving neoadjuvant chemoimmunotherapy reveals similar immune cell compositions between tpMLNs and tdMLNs. Notably, terminally differentiated exhausted CD8+ T lymphocytes (CD8+ Tex-term) in tumors share clonal lineages with CD8+ Tpex populations in both tpMLNs and tdMLNs. Multiplex immunofluorescence analysis confirms TOX+TCF-1+CXCL13+ CD8+ Tpex in both tpMLNs and tdMLNs, but not in primary tumors. Clonal tracking at 1, 6, and 18 months post-surgery detects both tumor-derived CD8+ Tex-term and CD8+ Tpex-related clones in peripheral blood. These findings suggest that tdMLNs perform immunological functions like tpMLNs in LUSC antitumor immune responses. Therefore, we propose preserving tdMLNs during surgical resection to maintain these immune effector cell reserves and support postoperative immunological competence and adjuvant therapeutic outcomes.
分类与指标
- 研究类型
- 基础研究
- 病种
- 肺癌
- JCR 分区
- Q1
- 影响因子
- 45.1
- 新锐分区
- 1区