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肿瘤浸润免疫细胞仅在未接受过药物治疗的生长激素瘤中预测对生长抑素受体配体的反应

英文原题:Tumor-infiltrating immune cells predict the response to somatostatin receptor ligands only in somatotropinomas naïve to medical therapy.

查看英文原题

Tumor-infiltrating immune cells predict the response to somatostatin receptor ligands only in somatotropinomas naïve to medical therapy.

PubMed 2025/08/11(内容时间) J Neuroendocrinol Q1 · IF 5(JCR 2025)

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中文摘要

肿瘤浸润免疫细胞(TICs)是肿瘤微环境(TME)的重要组成部分。它们通过可溶性因子和细胞因子调节生长激素细胞腺瘤对生长抑素受体配体(SRLs)治疗的反应。

在本研究中,我们评估了SRLs治疗对TICs的影响。我们进行了一项回顾性观察性研究,纳入肢端肥大症患者,比较了75例术前未接受过SRL治疗的患者与33例术前接受SRL治疗至少6个月的患者之间TICs的数量。在术前未接受过SRL治疗的患者中,侵袭性肿瘤的CD68+/CD8+比值(4.9,IQR:14,p = .028)高于非侵袭性肿瘤(4.3,IQR:4.2),对术后/辅助SRL治疗无反应的患者(7.5,IQR:13,p = .006)也高于有反应的患者(3.4,IQR:3.2)。在术前接受SRL治疗的患者中,对术后/辅助SRL治疗无反应的患者CD68+巨噬细胞数量和CD68+/CD8+比值(CD68+:48/HPFs,IQR:22.9,p = .005;CD68+/CD8+:2.0,IQR:3.6,p = .05)低于有反应的患者(CD68+:80/HFPs,IQR:51,CD68+/CD8+:5,IQR:5.6)。较高的CD68+/CD8+比值是术后SRL治疗耐药的独立危险因素,但仅在术前未接受过SRL治疗的患者中如此(OR:4.3,95% IC:1.4-12.9,p = .006)。

我们的结果表明,术前SRL治疗与生长激素细胞腺瘤中的TICs存在相互作用,并表明CD68+/CD8+比值是未接受过SRL治疗患者治疗耐药的生物标志物。临床试验注册:临床试验注册号为5116。

展开英文摘要原文

Tumor-infiltrating immune cells (TICs) are important components of the tumor microenvironment (TME). They regulate somatotroph adenoma treatment responses to therapy with somatostatin receptor ligands (SRLs), mediated by soluble factors and cytokines. In this study, we assessed the effect of SRLs treatment on TICs. A retrospective and observational study was performed on acromegaly patients to compare the number of TICs in 75 patients naïve to SRL before surgery and in 33 patients treated with SRL for at least 6 months before surgery. In SRLs-naive patients at surgery, the CD68+/CD8+ ratio was higher in invasive tumors (4. 9, IQR: 14, p = . 028) than in non-invasive tumors (4. 3, IQR: 4.

2) as well as in patients not responsive to post-surgical/adjuvant treatment with SRLs (7. 5, IQR: 13, p = . 006) than those responsive to treatment (3. 4, IQR: 3. 2). In patients treated with SRLs before surgery, the number of CD68+ macrophages and the ratio CD68+/CD8+ were lower in patients non-responsive to post-surgery/adjuvant SRL treatment (CD68+: 48/HPFs, IQR: 22.

9, p = . 005; CD68+/CD8+: 2. 0, IQR: 3. 6, p = . 05) than in responsive patients (CD68+: 80/HFPs, IQR: 51, CD68+/CD8+: 5, IQR: 5. 6). Higher CD68+/CD8+ ratio was an independent risk factor for post-surgery SRL treatment resistance, only in patients naïve to SRLs at surgery (OR: 4. 3, 95% IC: 1. 4-12. 9, p = . 006).

Our results indicate a presurgical SRL therapy interplay with TICs in somatotroph adenomas and show that the CD68+/CD8+ ratio is a biomarker for treatment resistance in SRL-naïve patients. CLINICAL TRIAL REGISTRATION: The Clinical Trial Registration number is 5116.

论文信息

作者
Chiloiro S、Vicari A、Giampietro A、Mattogno PP、Cappoli N、Konini G、Calandrelli R、Lauretti L
单位
Dipartimento di Endocrinologia, Fondazione Policlinico Universitario A. Gemelli, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy.Italy
文献类型
观察性研究 · 非美国政府资助研究
期刊
Journal of neuroendocrinology2025 Nov
原文标识
PubMed 40789673 · DOI 10.1111/jne.70078