研究概要
在本研究中,我们通过纳入近期活化的 CTL 的空间信息,在主要为白人女性的 HGSOC 中重复验证了与 OS 显著改善的关联。需要进一步研究以理解近期活化的空间结构影响 HGSOC 生存的机制。影响:本研究验证了我们之前的发现,即在生存分析中,将空间背景加入丰度分析,尤其是 CTL 或近期活化的 CTL,可改善模型的拟合度。
研究思路结论见上方概要
背景
既往研究发现,将TIL(肿瘤浸润淋巴细胞)和细胞毒性T淋巴细胞(CTL)的空间背景加入丰度信息后,可改善其与非西班牙裔黑人女性高级别浆液性卵巢癌(HGSOC)总生存期(OS)的关联。本研究旨在以非西班牙裔白人女性为主的HGSOC队列中重复既往发现。
方法
多重免疫荧光用于表征来自三项流行病学研究(N = 433)中入组女性的HGSOC中的TIL。TIL的空间聚类通过Ripley K的置换方法得出。Cox比例风险模型用于分析空间聚类和丰度与OS的关联。
结果
在评估TIL高丰度(>1%)肿瘤内空间聚集差异的模型中,我们发现空间信息显著改善了近期活化CTL的模型拟合(似然比检验P = 0.008),其中与近期活化CTL高度聚集相比,高丰度下低空间聚集与死亡风险降低相关(风险比 = 0.31;95%置信区间,0.14-0.70;P = 0.004)。
展开英文摘要原文
BACKGROUND
A previous study found that adding the spatial context of tumor-infiltrating lymphocytes (TIL) and cytotoxic T lymphocytes (CTL) to abundance improved associations with overall survival (OS) of non-Hispanic Black women with high-grade serous ovarian cancer (HGSOC). This study set out to replicate previous findings in predominantly non-Hispanic White women HGSOC cohorts.
METHODS
Multiplex immunofluorescence was used to characterize TILs in HGSOC from women enrolled in three epidemiologic studies (N = 433). Spatial clustering of TILs was derived using a permutation approach for Ripley K. Cox proportional hazards models were used for associations of spatial clustering and abundance with OS.
RESULTS
In models assessing differences in spatial clustering within tumors with a high abundance of TILs (>1%), we found that spatial information significantly improved the model fit for the recently activated CTLs (likelihood ratio test P = 0.008), in which low spatial clustering in high abundance was associated with a decreased risk of mortality (hazard ratio = 0.31; 95% confidence interval, 0.14-0.70; P = 0.004) compared with when the recently activated CTLs were highly clustered.
CONCLUSIONS
In this study, we replicated the significantly improved association with OS in mostly White women with HGSOC by including spatial information for the recently activated CTLs. Further research is needed to understand the mechanisms by which recently activated spatial architecture affects survival from HGSOC.
IMPACT: This study validates our previous findings that adding spatial context to abundance, especially CTLs or the recently activated CTLs, when performing survival analyses improves the fit of the models.
论文信息
- 作者
- Soupir AC、Townsend MK、Hathaway CA、Nguyen J、Moran Segura C、Saeed-Vafa D、Ospina OE、Peres LC
- 第一作者单位
- Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, Florida.United States
- 通讯作者单位
- Division of Health Services and Outcomes Research, Children's Mercy Hospital, Kansas City, Missouri.
- 期刊
- Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology2026 Apr 14