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晚期宫颈癌中肿瘤免疫浸润与全身免疫介质同治疗应答及预后的关联

英文原题:Linking tumor immune infiltrate and systemic immune mediators to treatment response and prognosis in advanced cervical cancer.

查看英文原题

Linking tumor immune infiltrate and systemic immune mediators to treatment response and prognosis in advanced cervical cancer.

PubMed 2023/12/19(内容时间) Sci Rep Q1 · IF 4.9(JCR 2025)

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中文摘要

宫颈癌(CC)给发展中地区人群带来沉重负担;患者对标准放化疗的应答存在异质性,死亡率也较高。阐明宿主免疫动态有望推动创新疗法及临床相关生物标志物的发现。

我们前瞻性研究局部晚期CC患者治疗前的状态,并将其分为应答者(R)和未应答者(NR)。R患者TIL(肿瘤浸润淋巴细胞)增加;NR患者PD-1评分、CD8+及PD-L2+ TIL和PD-L1免疫反应性升高。NR患者系统性可溶性介质水平较高,并与TIL免疫标志物相关。R患者CD4 T细胞呈现功能性极化(Th1、Th2、Th17和Treg),而NR组以CD8+ T细胞和CD68+巨噬细胞为主。受试者工作特征分析确定了潜在的CC治疗应答预测因子,包括PD-L1免疫反应性(IR)区域、PD-L2、CD8、碱性成纤维细胞生长因子(FGF-basic)、IL-7、IL-8、IL-12p40、IL-15和TNF-α。功能失调的TIL及免疫介质失衡会导致治疗不足,并揭示局部与全身免疫之间的相互作用。本研究为治疗预测和CC预后的免疫学特征提供参考。

展开英文摘要原文

Cervical cancer (CC) poses a significant burden on individuals in developing regions, exhibiting heterogeneous responses to standard chemoradiation therapy, and contributing to substantial mortality rates. Unraveling host immune dynamics holds promise for innovative therapies and discovery of clinically relevant biomarkers.

We studied prospectively locally advanced CC patients pre-treatment, stratifying them as responders (R) or non-responders (NR). R patients had increased tumor-infiltrating lymphocytes (TILs), while NR patients showed elevated PD-1 scores, CD8+ and PD-L2+ TILs, and PD-L1 immune reactivity. NR patients exhibited higher systemic soluble mediators correlating with TIL immune markers.

R patients demonstrated functional polarization of CD4 T cells (Th1, Th2, Th17, and Treg), while CD8+ T cells and CD68+ macrophages predominated in the NR group. Receiver operating characteristic analysis identified potential CC response predictors, including PD-L1-immunoreactive (IR) area, PD-L2, CD8, FGF-basic, IL-7, IL-8, IL-12p40, IL-15, and TNF-alpha. Dysfunctional TILs and imbalanced immune mediators contribute to therapeutic insufficiency, shedding light on local and systemic immune interplay.

Our study informs immunological signatures for treatment prediction and CC prognosis.

论文信息

作者
Rocha Martins P、Luciano Pereira Morais K、de Lima Galdino NA、Jacauna A、Paula SOC、Magalhães WCS、Zuccherato LW、Campos LS
第一作者单位
Pathology Department, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.Brazil
通讯作者单位
Instituto Mário Penna, Belo Horizonte, MG, Brazil. kenneth.gollob@einstein.br.Brazil
期刊
Scientific reports2023 Dec 19
原文标识
PubMed 38114557 · DOI 10.1038/s41598-023-49441-2