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新辅助化疗对卵巢癌肿瘤微环境的影响:文献系统综述

英文原题:The Impact of Neoadjuvant Chemotherapy on Ovarian Cancer Tumor Microenvironment: A Systematic Review of the Literature.

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The Impact of Neoadjuvant Chemotherapy on Ovarian Cancer Tumor Microenvironment: A Systematic Review of the Literature.

PubMed 2024/06/27(内容时间) Int J Mol Sci Q1 · IF 5.6(JCR 2025)

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中文摘要

免疫治疗,尤其是免疫检查点抑制剂(ICIs)的应用,在治疗卵巢癌(OC)方面显示出有限的疗效,这可能与肿瘤微环境中多样的T细胞浸润模式有关。本综述探讨了新辅助化疗(NACT)如何影响OC的免疫景观,重点关注TIL(肿瘤浸润淋巴细胞)(TILs)、PD-1/PD-L1表达及其临床意义。在四个数据库中进行全面文献检索,共获得九项相关研究。这些研究评估了NACT前后基质(sTILs)和上皮内(ieTILs)TILs。sTIL反应各异,影响预后结局,而ieTILs在一些患者中增加,但与生存关联不明确。NACT后PD-L1表达与改善的总生存期(OS)相关,颗粒酶B+和PD-1的增加与更长的无进展生存期(PFS)相关。

值得注意的是,NACT后FoxP3+ TILs减少与更好的预后相关。NACT通常增加sTIL/ieTIL和CD8+亚群,但它们与改善PFS和OS的相关性不一。共抑制分子上调,尤其是PD-L1,提示对化疗的免疫抑制反应。正在进行的探索新辅助ICIs和化疗的试验为推进OC治疗带来了希望。标准化测量评估TIL密度、位置和异质性对于应对OC的遗传复杂性和免疫异质性至关重要。

展开英文摘要原文

Immunotherapy, particularly the use of immune checkpoint inhibitors (ICIs), has shown limited efficacy in treating ovarian cancer (OC), possibly due to diverse T cell infiltration patterns in the tumor microenvironment. This review explores how neoadjuvant chemotherapy (NACT) impacts the immune landscape of OC, focusing on tumor-infiltrating lymphocytes (TILs), PD-1/PD-L1 expression, and their clinical implications. A comprehensive literature search across four databases yielded nine relevant studies. These studies evaluated stromal (sTILs) and intra-epithelial (ieTILs) TILs before and after NACT. sTIL responses varied, impacting prognostic outcomes, and ieTILs increased in some patients without clear survival associations.

PD-L1 expression after NACT correlated with improved overall survival (OS), and increases in granzyme B+ and PD-1 correlated with longer progression-free survival (PFS). Remarkably, reduced FoxP3+ TILs post-NACT correlated with better prognosis. NACT often increases sTIL/ieTIL and CD8+ subpopulations, but their correlation with improved PFS and OS varies.

Upregulation of co-inhibitory molecules, notably PD-L1, suggests an immunosuppressive response to chemotherapy. Ongoing trials exploring neoadjuvant ICIs and chemotherapy offer promise for advancing OC treatment. Standardized measurements assessing TIL density, location, and heterogeneity are crucial for addressing genetic complexity and immunological heterogeneity in OC.

论文信息

作者
Spagnol G、Ghisoni E、Morotti M、De Tommasi O、Marchetti M、Bigardi S、Tuninetti V、Tasca G
第一作者单位
Unit of Gynecology and Obstetrics, Department of Women and Children's Health, University of Padua, 35122 Padua, Italy.Italy
通讯作者单位
Department of Oncology, Lausanne University Hospital, University of Lausanne (UNIL), 1015 Lausanne, Switzerland.Switzerland
文献类型
系统综述
期刊
International journal of molecular sciences2024 Jun 27
原文标识
PubMed 39000178 · DOI 10.3390/ijms25137070