CELL INTELLIGENCE · 肿瘤细胞治疗研究

CELLIN 肿瘤细胞治疗研究

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血清 IL-6 和 NK-T 细胞升高与 HER2 阳性乳腺癌接受含卡铂新辅助治疗后病理完全缓解率增加相关

英文原题：Elevated Sera IL-6 and NK-T Cells Associated With Increased Pathological Complete Response in HER2-positive Breast Cancer With Carboplatin-based Neoadjuvant Therapy.

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Elevated Sera IL-6 and NK-T Cells Associated With Increased Pathological Complete Response in HER2-positive Breast Cancer With Carboplatin-based Neoadjuvant Therapy.

PubMed 2023/04/01（内容时间） Altern Ther Health Med

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靶点：HER2技术：NK 细胞乳腺癌
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研究概要

免疫因素，包括 IL-6、NK-T 细胞、CD4+ T 与 CD8+ T 比值以及 TILs 表达，是 TCbH 新辅助治疗联合卡铂应答的重要预测因素。

研究思路结论见上方概要

背景

新辅助治疗是II至III期乳腺癌（BC）的主要治疗手段。BC的异质性给确定有效的新辅助方案及相关敏感人群带来了挑战。

目的

本研究旨在探讨炎症细胞因子、免疫细胞亚群和TIL（肿瘤浸润淋巴细胞）（TILs）对新辅助方案后达到病理完全缓解（pCR）的预测作用。

方法

研究团队开展了一项II期、单臂、开放标签试验。研究地点位于中国河北石家庄的河北医科大学第四医院。参与者为2018年11月至2021年期间在该院接受人表皮生长因子受体2（HER2）阳性乳腺癌（BC）治疗的42例患者。参与者接受了六个周期的多西他赛、卡铂和曲妥珠单抗（TCbH）新辅助治疗。结局指标：研究团队：（1）在新辅助治疗给药前测量了外周血中的13种细胞因子和免疫细胞群体；（2）测量了肿瘤组织中的TILs；（3）分析了生物标志物与pCR之间的相关性。

结果

在42名参与者中，18名在新辅助治疗后达到pCR（42.9%），37名的总体缓解率（ORR）为88.1%。所有参与者均经历了至少一次短期不良事件。最常见的毒性是白细胞减少，有33名参与者（78.6%），而未发生心血管功能障碍。与非pCR组相比，pCR组的血清肿瘤坏死因子α（TNF-ɑ）水平较高，P = .013；白细胞介素6（IL-6），P = .025；以及IL-18，P = .0004。单变量分析显示，IL-6（OR，3.429；95% CI，1.838-6.396；P = .0001）与pCR有显著相关性。pCR组的参与者在新辅助治疗前自然杀伤T（NK-T）细胞水平较高（P = .009），且分化簇4（CD4）:CD8比值较低（P = .0014）。单变量分析将高NK-T细胞群体（OR，0.204；95% CI，0.052-0.808；P = .018）、低CD4:CD8比值（OR，10.500；95% CI，2.475-44.545；P = .001）和TILs表达（OR，0.192；95% CI，0.051-0.731；P = .013）与pCR联系起来。

展开英文摘要原文
OBJECTIVE

The study intended to explore the predictive role of inflammatory cytokines, immune-cell subsets, and tumor-infiltrating lymphocytes (TILs) for the accomplishment of the pathological complete response (pCR) after a neoadjuvant regimen. DESIGN: The research team conducted a phase II, single-armed, open-label trial. SETTING: The study took place at the Fourth Hospital of Hebei Medical University in Shijiazhuang, Hebei, China. PARTICIPANTS: Participants were 42 patients at the hospital receiving treatment for human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) between November 2018 and October 2021. INTERVENTION: Participants received neoadjuvant therapy of six cycles of docetaxel, carboplatin, and trastuzumab (TCbH). OUTCOME MEASURES: The research team: (1) measured 13 cytokines and immune-cell populations in peripheral blood prior to neoadjuvant therapy administration; (2) measured TILs in tumor tissues; (3) analyzed correlations among biomarkers and pCR.

RESULTS

Of the 42 participants, 18 achieved pCR (42.9%) after the neoadjuvant therapy, with 37 having an overall response rate (ORR) of 88.1%. All participants experienced at least one short-term adverse event. The most common toxicity was leukopenia, with 33 participants (78.6%), while no cardiovascular dysfunction occurred. Compared with the non-pCR group, the pCR group had higher serum levels of tumor necrosis factor alpha (TNF-ɑ), with P = .013; interleukin 6 (IL-6), with P = .025; and IL-18, with P = .0004. Univariate analysis showed that IL-6 (OR, 3.429; 95% CI,1.838-6.396; P = .0001) had a significant correlation with pCR. Participants in the pCR group had a higher level of natural killer T (NK-T) cells (P = .009) and a lower ratio of cluster of differentiation 4 (CD4):CD8 (P = .0014) before neoadjuvant therapy. Univariate analysis linked a high population of NK-T cells (OR, 0.204; 95% CI,0.052-0.808; P = .018), a low CD4:CD8 ratio (OR, 10.500; 95% CI, 2.475-44.545; P = .001), and TILs expression (OR, 0.192; 95% CI, 0.051-0.731; P = .013) to pCR.

CONCLUSIONS

Immunological factors, including IL-6, NK-T cells, CD4+ T versus CD8+ T ratio, and TILs expression were significant predictors for response to TCbH neoadjuvant therapy with carboplatin.

论文信息

作者
Wang L、Zhang X、Ma X、Ren X、Ma X、Shan B、Liu Y
期刊
Alternative therapies in health and medicine2023 Apr
原文标识
PubMed 36881538

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