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非小细胞肺癌中 TIL(肿瘤浸润淋巴细胞)的扩增:EGFR 突变亚群中的临床潜力和疗效

英文原题:Expansion of tumor-infiltrating lymphocytes in non-small cell lung cancer: Clinical potential and efficacy in EGFR mutation subsets.

PubMed 2024/06/20(内容时间) Clin Immunol Q2 · IF 4.1(JCR 2025)

研究概要

在快速扩增方案(REP)后的 TILs 中,16 例中有 13 例,包括所有 3 例 EGFR 突变病例,表现出 IFN- 分泌增加两倍或以上。

中文摘要

本研究旨在扩增原发性非小细胞肺癌中的TIL(肿瘤浸润淋巴细胞),并评估其对肿瘤细胞的反应性。研究对103例肿瘤进行扩增,并通过组织病理学、流式细胞术、干扰素γ释放、细胞毒性实验和体内实验进行评估。无论EGFR突变状态如何,均可扩增TIL。快速扩增后的TIL中,16例有13例的干扰素γ分泌至少增加一倍,其中包括全部3例EGFR突变病例;部分病例的肿瘤细胞杀伤增强。患者来源异种移植模型的体内功能实验显示肿瘤体积减小。快速扩增后TIL的抗肿瘤活性提示其可能成为晚期非小细胞肺癌的治疗选择,且不受突变状态限制。

展开英文摘要原文

Our study aimed to expand tumor-infiltrating lymphocytes (TILs) from primary non-small cell lung cancers (NSCLCs) and evaluate their reactivity against tumor cells. We expanded TILs from 103 primary NSCLCs using histopathological analysis, flow cytometry, IFN- release assays, cell-mediated cytotoxicity assays, and in vivo efficacy tests. TIL expansion was observed in all cases, regardless of EGFR mutation status. There was also an increase in the median CD4 + /CD8 + ratio during expansion. In post-rapid expansion protocol (REP) TILs, 13 out of 16 cases, including all three cases with EGFR mutations, exhibited a two-fold or greater increase in IFN- secretion. The cytotoxicity assay revealed enhanced tumor cell death in three of the seven cases, two of which had EGFR mutations. In vivo functional testing in a patient-derived xenograft model showed a reduction in tumor volume. The anti-tumor activity of post-REP TILs underscores their potential as a therapeutic option for advanced NSCLC, irrespective of mutation status.

论文信息

作者
Lee H、Lee M、Lim CL、Park HS、Song IH、Jeong BK、Kim DK、Kim YH
第一作者单位
Department of Pathology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.South Korea
通讯作者单位
Research and Development Center, NeogenTC Corp., Seoul, Republic of Korea; Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. Electronic address: backlila1@amc.seoul.kr.South Korea
期刊
Clinical immunology (Orlando, Fla.)2024 Aug
原文标识
PubMed 38908769 · DOI 10.1016/j.clim.2024.110289