新辅助靶向治疗对可切除肺腺癌肿瘤微环境的影响。

IF 4.8 2区医学 Q1 Medicine

Cellular Oncology Pub Date : 2025-08-27 DOI:10.1007/s13402-025-01101-5

Ling Yi, Heng Yao, Zhexin Bai, Ziwei Xu, Huimin Li, Yuting Cheng, Chong Wang

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All patients received R0 resection, and thoracoscopic minimally invasive surgery were the predominant method. Seven (16.7%) patients reached pathological complete response (pCR), 4 (9.5%) get major pathological response (MPR), and these 11 patients were classified into the MPR group. The remaining 31 (73.8%) patients were non-MPR. The densities of CD8 + T cells (P < 0.001, P = 0.001), GZMB + CD8 + T cells (P = 0.004, P = 0.008), PD-1 + CD8 + T cells (P = 0.019, P = 0.036), macrophages (P = 0.020, P = 0.007), M1 macrophages (P = 0.010, P = 0.007), and ratios of CD8 + T/Treg (P < 0.001, P = 0.026) in TME were significantly higher in the MPR group and ALK mutation group compared with non-MPR and EGFR group. There were positive correlations between CD8 + T cells, PD-1 + CD8 + T cells (r = 0.397, P = 0.009) and GZMB + CD8 + T cells (r = 0.351, P = 0.023); CD8 + T cells and macrophages (r = 0.343, P = 0.026), and M1 macrophages (r = 0.412, P = 0.007). 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引用次数: 0

摘要

背景：新辅助靶向治疗已成为可切除的非小细胞肺癌（NSCLC）的一种有前景的治疗策略。分析靶向治疗后肿瘤微环境（tumor microenvironment， TME）的免疫状态，对于了解靶向治疗对TME的影响，为制定协同治疗方案提供依据至关重要。方法：选取42例可切除肺腺癌（LUAD）患者为研究对象，采用多重免疫荧光技术探讨新辅助靶向治疗后TME的免疫状态。结果：42例患者中ALK和EGFR突变分别为9例（21.4%）和33例（78.6%），TKIs是其一线治疗方案。所有患者均行R0切除，以胸腔镜微创手术为主。7例（16.7%）患者达到病理完全缓解（pCR）， 4例（9.5%）患者达到主要病理缓解（MPR），将这11例患者归入MPR组。其余31例（73.8%）为非mpr。结论：tki靶向治疗可减轻肿瘤负担，促进手术完全切除。MPR和ALK突变患者TME中炎症免疫细胞密度较高，巨噬细胞密度较高的患者PFS明显延长。临床试验号：不适用。

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Effect of neoadjuvant targeted therapy on the tumor microenvironment in resectable lung adenocarcinoma.

Background: Neoadjuvant targeted therapy has emerged as a promising strategy for resectable non-small cell lung cancer (NSCLC). The analysis of the immune status of tumor microenvironment (TME) after targeted therapies is crucial for understanding the impact of targeted therapy on the TME and providing a basis for synergistic therapeutic approaches.

Methods: Forty-two patients with resectable lung adenocarcinoma (LUAD) were enrolled in this study, and multiplex immunofluorescence technology was used to explore the immune status of the TME after neoadjuvant targeted therapies.

Results: Among the 42 patients, 9 (21.4%) and 33 (78.6%) had ALK and EGFR mutations, respectively, and TKIs were their first-line treatment. All patients received R0 resection, and thoracoscopic minimally invasive surgery were the predominant method. Seven (16.7%) patients reached pathological complete response (pCR), 4 (9.5%) get major pathological response (MPR), and these 11 patients were classified into the MPR group. The remaining 31 (73.8%) patients were non-MPR. The densities of CD8 + T cells (P < 0.001, P = 0.001), GZMB + CD8 + T cells (P = 0.004, P = 0.008), PD-1 + CD8 + T cells (P = 0.019, P = 0.036), macrophages (P = 0.020, P = 0.007), M1 macrophages (P = 0.010, P = 0.007), and ratios of CD8 + T/Treg (P < 0.001, P = 0.026) in TME were significantly higher in the MPR group and ALK mutation group compared with non-MPR and EGFR group. There were positive correlations between CD8 + T cells, PD-1 + CD8 + T cells (r = 0.397, P = 0.009) and GZMB + CD8 + T cells (r = 0.351, P = 0.023); CD8 + T cells and macrophages (r = 0.343, P = 0.026), and M1 macrophages (r = 0.412, P = 0.007). Additionally, eleven patients experienced disease progress during the follow-up period, and the Log-Rank test revealed that MPR patients tended to get longer PFS compared with non-MPR patients (P = 0.063), especially patients with higher densities of macrophages in the TME had significantly longer PFS (P = 0.042).

Conclusion: TKI-targeted therapy could reduce tumor burden, facilitating complete surgical resection. Patients with MPR and ALK mutations had a higher density of inflammatory immune cells in the TME and those with higher densities of macrophage had significantly longer PFS.

Clinical trial number: Not applicable.

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来源期刊

Cellular Oncology Biochemistry, Genetics and Molecular Biology-Cancer Research

CiteScore

10.40

自引率

1.50%

发文量

审稿时长

16 weeks

期刊介绍： The Official Journal of the International Society for Cellular Oncology Focuses on translational research Addresses the conversion of cell biology to clinical applications Cellular Oncology publishes scientific contributions from various biomedical and clinical disciplines involved in basic and translational cancer research on the cell and tissue level, technical and bioinformatics developments in this area, and clinical applications. This includes a variety of fields like genome technology, micro-arrays and other high-throughput techniques, genomic instability, SNP, DNA methylation, signaling pathways, DNA organization, (sub)microscopic imaging, proteomics, bioinformatics, functional effects of genomics, drug design and development, molecular diagnostics and targeted cancer therapies, genotype-phenotype interactions. A major goal is to translate the latest developments in these fields from the research laboratory into routine patient management. To this end Cellular Oncology forms a platform of scientific information exchange between molecular biologists and geneticists, technical developers, pathologists, (medical) oncologists and other clinicians involved in the management of cancer patients. In vitro studies are preferentially supported by validations in tumor tissue with clinicopathological associations.