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HER2+乳腺癌患者接受化疗联合曲妥珠单抗联合帕妥珠单抗新辅助治疗的外周免疫特征深入分析

英文原题:In-Depth Analysis of the Peripheral Immune Profile of HER2+ Breast Cancer Patients on Neoadjuvant Treatment with Chemotherapy Plus Trastuzumab Plus Pertuzumab.

PubMed 2024/08/27(内容时间) Int J Mol Sci Q1 · IF 5.6(JCR 2025)

研究概要

达到的病理完全缓解(pCR)率为82.3%。

中文摘要

目前,早期人表皮生长因子受体2阳性(HER2+)乳腺癌(BC)的治疗基于曲妥珠单抗和帕妥珠单抗联合化疗的新辅助方案。INMUNOHER研究旨在检测外周血中的免疫标志物及其与治疗反应的关系。共招募了62例HER2+ BC患者。治疗前样本在治疗开始前获取,治疗后样本在完成治疗及手术前获取,并通过流式细胞术进行分析。达到的病理完全缓解(pCR)率为82.3%。在未达到pCR的患者中,Natural Killer(NK)-CD56dim亚群中NKp30、PD-1和TIM-3受体的表达降低。治疗后,白细胞中发现了许多变化,包括T细胞淋巴细胞比例的改变。此外,NK细胞的百分比下降,并在该群体中观察到若干表型变化。治疗后,NK细胞针对HER2+细胞(无论是否联合曲妥珠单抗)的IFN-γ产生显著减少。HER2靶向治疗联合化疗在大多数患者中显示出高效性,降低了发现免疫标志物的统计效能。然而,NK亚群表型与反应组的关联性更好,并且在大多数患者治疗后观察到白细胞以及T细胞和NK细胞百分比的众多变化,以及NK细胞功能的变化,这鼓励了对这些免疫群体的进一步研究。

展开英文摘要原文

Currently, therapy for early-stage human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC) is based on the combination of trastuzumab and pertuzumab plus chemotherapy in a neoadjuvant regimen. The INMUNOHER study aimed to detect immunological markers in peripheral blood and their association with treatment response. Sixty-two HER2+ BC patients were recruited. Pre-treatment samples were obtained before the start of treatment, while post-treatment samples were obtained after completing therapy and before surgery and were analyzed by flow cytometry. The pathologic complete response (pCR) rate achieved was 82.3%. The expression of the NKp30, PD-1, and TIM-3 receptors was reduced in the Natural Killer (NK)-CD56dim subset of patients who did not achieve pCR. Following therapy, many changes were found in leukocytes, including alterations in T cell lymphocyte proportions. Also, the percentage of NK cells decreased, and several phenotypic changes were observed in this population. After treatment, IFN-γ production by NK cells against HER2+-cells with or without trastuzumab was significantly reduced. HER2-targeted therapy plus chemotherapy demonstrated high efficacy in most patients, reducing the statistical power for finding immunological markers. However, NK subset phenotypes correlated better with response groups, and numerous changes in the percentage of leukocytes and T and NK cells, as well as changes in the functionality of NK cells, were observed in most patients after treatment, encouraging further research into these immune populations.

论文信息

作者
Pesce Viglietti AI、Bordignon MB、Ostinelli A、Rizzo MM、Cueto G、Sanchez MB、Perazzo F、Amat M
单位
Centro de Investigaciones Oncológicas (FUCA), Fundación Cáncer, Ciudad Autónoma de Buenos Aires C1426AOE, Argentina.Argentina
期刊
International journal of molecular sciences2024 Aug 27
原文标识
PubMed 39273217 · DOI 10.3390/ijms25179268