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种族差异对高级别浆液性卵巢癌女性肿瘤免疫全景和生存的影响。

Racial Differences in the Tumor Immune Landscape and Survival of Women with High-Grade Serous Ovarian Carcinoma.

机构信息

Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.

Department of Surgery, Duke University School of Medicine, Durham, North Carolina.

出版信息

Cancer Epidemiol Biomarkers Prev. 2022 May 4;31(5):1006-1016. doi: 10.1158/1055-9965.EPI-21-1334.

Abstract

BACKGROUND

Tumor-infiltrating lymphocytes (TIL) confer a survival benefit among patients with ovarian cancer; however, little work has been conducted in racially diverse cohorts.

METHODS

The current study investigated racial differences in the tumor immune landscape and survival of age- and stage-matched non-Hispanic Black and non-Hispanic White women with high-grade serous ovarian carcinoma (HGSOC) enrolled in two population-based studies (n = 121 in each racial group). We measured TILs (CD3+), cytotoxic T cells (CD3+CD8+), regulatory T cells (CD3+FoxP3+), myeloid cells (CD11b+), and neutrophils (CD11b+CD15+) via multiplex immunofluorescence. Multivariable Cox proportional hazard regression was used to estimate the association between immune cell abundance and survival overall and by race.

RESULTS

Overall, higher levels of TILs, cytotoxic T cells, myeloid cells, and neutrophils were associated with better survival in the intratumoral and peritumoral region, irrespective of tissue compartment (tumor, stroma). Improved survival was noted for T-regulatory cells in the peritumoral region and in the stroma of the intratumoral region, but no association for intratumoral T-regulatory cells. Despite similar abundance of immune cells across racial groups, associations with survival among non-Hispanic White women were consistent with the overall findings, but among non-Hispanic Black women, most associations were attenuated and not statistically significant.

CONCLUSIONS

Our results add to the existing evidence that a robust immune infiltrate confers a survival advantage among women with HGSOC; however, non-Hispanic Black women may not experience the same survival benefit as non-Hispanic White women with HGSOC.

IMPACT

This study contributes to our understanding of the immunoepidemiology of HGSOC in diverse populations.

摘要

背景

肿瘤浸润淋巴细胞(TIL)可使卵巢癌患者获益,但在种族多样化的队列中,相关研究较少。

方法

本研究调查了年龄和分期匹配的非西班牙裔黑人(NHB)和非西班牙裔白人(NHW)患有高级别浆液性卵巢癌(HGSOC)的患者的肿瘤免疫景观和生存的种族差异,这些患者来自两项基于人群的研究(每组种族各 121 例)。我们通过多重免疫荧光法测量 TIL(CD3+)、细胞毒性 T 细胞(CD3+CD8+)、调节性 T 细胞(CD3+FoxP3+)、髓样细胞(CD11b+)和中性粒细胞(CD11b+CD15+)。多变量 Cox 比例风险回归用于估计免疫细胞丰度与总生存率和种族之间的关系。

结果

总体而言,肿瘤内和肿瘤旁区域中 TIL、细胞毒性 T 细胞、髓样细胞和中性粒细胞水平较高与生存时间延长相关,与组织区室(肿瘤、基质)无关。在肿瘤旁区域和肿瘤内基质的调节性 T 细胞中观察到更好的生存,而肿瘤内调节性 T 细胞则没有关联。尽管不同种族群体的免疫细胞丰度相似,但在 NHW 女性中与生存相关的关联与总体发现一致,但在 NHB 女性中,大多数关联减弱且无统计学意义。

结论

我们的研究结果增加了现有证据,即强大的免疫浸润可使 HGSOC 女性获益,但 NHB 女性可能不会像 HGSOC 的 NHW 女性那样获得相同的生存获益。

影响

这项研究有助于我们了解不同人群中 HGSOC 的免疫流行病学。

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