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头颈部鳞状细胞癌来源 TIL(肿瘤浸润淋巴细胞)的扩增以评估过继细胞治疗的潜力

英文原题:Expansion of tumor-infiltrating lymphocytes from head and neck squamous cell carcinoma to assess the potential of adoptive cell therapy.

PubMed 2024/04/17(内容时间) Cancer Immunol Immunother Q1 · IF 5.8(JCR 2025)

研究概要

我们能够从约三分之一的 HNSCC 样本中扩增出 TIL。

中文摘要

背景与目的:体外扩增TIL(肿瘤浸润淋巴细胞)并过继转移,已能使多种恶性肿瘤消退。本研究评估头颈部鳞状细胞癌(HNSCC)样本中TIL的扩增产量、成功扩增的影响因素及免疫表型。 方法:从47份手术切除的HNSCC标本及其转移淋巴结中扩增TIL。将癌组织切成1–2 mm小块,初始扩增2周。分析肿瘤部位、吸烟史、间质TIL百分比、人乳头瘤病毒感染及程序性死亡配体1评分对TIL成功扩增的影响。使用流式细胞术评估扩增后TIL;对成功扩增的部分样本按快速扩增方案进行第二轮扩增。 结果:36.2%的样本成功扩增出TIL。扩增失败原因为污染(27.6%)或扩增不足(36.2%)。仅间质TIL百分比与成功扩增显著相关(p=0.032);间质TIL百分比还与每个组织块扩增所得TIL数量相关(r=0.341,p=0.048)。对成功扩增的13份样本进行流式分析,69.2%的病例以CD4⁺ T细胞为主。所有病例中,扩增后CD4⁺和CD8⁺ T细胞的主要表型均为效应记忆T细胞。 结论:约三分之一HNSCC样本可成功扩增TIL。这种扩增方法可能适用于临床病理特征多样的HNSCC样本。

展开英文摘要原文

BACKGROUND: Adoptive transfer of in vitro expanded tumor-infiltrating lymphocytes (TILs) has been effective in regressing several types of malignant tumors. This study assessed the yield and factors influencing the successful expansion of tumor-infiltrating lymphocytes (TILs) from head and neck squamous cell carcinoma (HNSCC), along with their immune phenotypes. METHODS: TILs were expanded from 47 surgically resected HNSCC specimens and their metastasized lymph nodes. The cancer tissues were cut into small pieces (1-2 mm) and underwent initial expansion for 2 weeks. Tumor location, smoking history, stromal TIL percentage, human papillomavirus infection, and programmed death-ligand 1 score were examined for their impact on successful expansion of TILs. Expanded TILs were evaluated by flow cytometry using fluorescence-activated cell sorting. A second round of TIL expansion following the rapid expansion protocol was performed on a subset of samples with successful TIL expansion. RESULTS: TILs were successfully expanded from 36.2% samples. Failure was due to contamination (27.6%) or insufficient expansion (36.2%). Only the stromal TIL percentage was significantly associated with successful TIL expansion (p = 0.032). The stromal TIL percentage also displayed a correlation with the expanded TILs per fragment (r = 0.341, p = 0.048). On flow cytometry analysis using 13 samples with successful TIL expansion, CD4 + T cell dominancy was seen in 69.2% of cases. Effector memory T cells were the major phenotype of expanded CD4 + and CD8 + T cells in all cases. CONCLUSION: We could expand TILs from approximately one-third of HNSCC samples. TIL expansion could be applicable in HNSCC samples with diverse clinicopathological characteristics.

论文信息

作者
Choi S、Hossain M、Lee H、Baek J、Park HS、Lim CL、Han D、Park T
第一作者单位
Department of Pathology, Brain Korea 21 project, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro, 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.South Korea
通讯作者单位
Department of Pathology, Brain Korea 21 project, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro, 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea. backlila@gmail.com.South Korea
期刊
Cancer immunology, immunotherapy : CII2024 Apr 17
原文标识
PubMed 38630265 · DOI 10.1007/s00262-024-03691-9