PO.IM01.04 · 免疫学
高级别浆液性卵巢癌铂类化疗后肿瘤微环境中MAVS表达和T细胞浸润的变化
Changes in MAVS expression and T-cell infiltration in the tumor microenvironment following platinum-based chemotherapy in high-grade serous ovarian carcinoma
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摘要 Abstract
中文摘要
背景：高级别浆液性卵巢癌（HGSC）对免疫检查点抑制剂（ICI）敏感性低，部分原因是肿瘤浸润T细胞有限。来自肿瘤细胞的I型干扰素（IFN）可能增强T细胞浸润。我们研究了MAVS（线粒体抗病毒信号蛋白）作为HGSC中I型IFN信号的诱导物，并分析了其与免疫细胞浸润在紫杉醇/卡铂（TC）治疗和预后方面的关联。
方法：我们首先纳入了本机构接受新辅助TC治疗后行间歇性肿瘤细胞减灭术（IDS）的晚期HGSC病例。收集配对的治疗前活检和IDS标本进行免疫组化，以评估癌细胞中的MAVS表达以及CD8⁺/CD4⁺ T细胞浸润。分析了TC治疗前后MAVS表达和T细胞浸润的变化，以及它们与TC敏感性的相关性。接下来，使用人HGSC细胞系，我们评估了铂类给药后MAVS表达和T细胞浸润的变化。最后，我们建立了ID8小鼠模型，将小鼠分为顺铂治疗组和对照组，以比较腹水产生率和体重变化。我们还比较了两组间腹水中的免疫细胞谱（如CD4⁺和CD8⁺ T细胞）以及肿瘤细胞中的MAVS表达。
结果：我们分析了2019年12月1日至2025年8月31日期间接受治疗的45例病例。大多数病例在TC治疗后MAVS表达增加，且此增加与CD8⁺ T细胞浸润增强相关。在预后分析中，TC治疗后MAVS表达降低与不良预后特征相关。在细胞系实验中，铂类处理的细胞系中MAVS表达增强，经Western印迹证实。在ID8小鼠模型中，顺铂治疗组的腹水产生率更快。我们还可视化了该组腹水中免疫细胞的比例。经Western印迹证实，来自该模型的肿瘤细胞在顺铂治疗组中同样表现出MAVS表达增加。
结论：在HGSC中，TC治疗诱导的MAVS表达变化可能有助于诱导CD8⁺ T细胞浸润。在体内，铂类给药同样提示MAVS表达和免疫细胞浸润的潜在改变。MAVS可能作为HGSC的ICI治疗中患者选择的生物标志物。
查看英文原文 English abstract
Background: High-grade serous ovarian carcinoma (HGSC) exhibits low sensitivity to immune checkpoint inhibitors (ICIs), partly due to limited tumor-infiltrating T cells. Type-I interferons (IFNs) from tumor cells may enhance T-cell infiltration. We investigated MAVS (mitochondrial antiviral-signaling protein) as an inducer of Type-I IFN signaling in HGSC and analyzed its association with immune-cell infiltration in relation to paclitaxel/carboplatin (TC) therapy and prognosis.
Methods: We first included advanced HGSC cases at our institution that underwent interval debulking surgery (IDS) following neoadjuvant TC therapy. Paired pre-treatment biopsies and IDS specimens were collected for immunohistochemistry to evaluate MAVS expression in cancer cells and CD8⁺/CD4⁺ T-cell infiltration. Changes in MAVS expression and T-cell infiltration before and after TC therapy were analyzed, along with their correlation with sensitivity to TC. Next, using human HGSC cell lines, we assessed changes in MAVS expression and T-cell infiltration following platinum administration. Finally, we established an ID8 mouse model and divided mise into a cisplatin-treated group and a control group to compare the rate of ascites production and changes in body weight. We also compared immune-cell profiles in ascites (e.g., CD4⁺ and CD8⁺ T cells) and MAVS expression in tumor cells between each groups.
Results: We analyzed 45 cases treated from December 1, 2019 to August 31, 2025. MAVS expression increased after TC therapy in most cases, and this increase correlated with enhanced CD8⁺ T-cell infiltration. In prognostic analyses, decreased MAVS expression after TC therapy was associated with poor prognostic features.
In cell line experiments, MAVS expression was enhanced in platinum-treated cell lines, as demonstrated by Western blotting.
In the ID8 mouse model, the rate of ascites production was faster in the cisplatin-treated group. We also visualized the proportions of immune cells within ascites in this group. Tumor cells derived from this model likewise exhibited increased MAVS expression in the cisplatin-treated group, as demonstrated by Western blotting.
Conclusions: In HGSC, TC therapy-induced changes in MAVS expression may contribute to the induction of CD8⁺ T-cell infiltration. In vivo, platinum administration similarly suggested potential alterations in MAVS expression and immune-cell infiltration. MAVS may serve as a biomarker for patient selection in ICI therapy for HGSC.
利益披露 Disclosure
Y. Yasui, None..
E. Nakatsuka, None..
Y. Shimizu, None..
M. Sakata, None..
Y. Takemoto, None..
G. Yamamoto, None..
A. Shimizu, None..
M. Kawano, None..
Y. Kinose, None..
K. Sawada, None..
M. Kodama, None.