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肯尼亚乳腺癌患者的肿瘤浸润淋巴细胞(TILs)和免疫组成:空间分布及与危险因素和肿瘤特征的关联。

Tumour Infiltrating Lymphocytes (TILs) and immune composition in breast cancer patients from Kenya: Spatial distributions and associations with risk factors and tumour characteristics.

机构信息

Department of Pathology, Aga Khan University, East Africa, P.O Box30270- 00100, Nairobi, Kenya.

Division of Anatomical Pathology, University of Cape Town, Cape Town, South Africa.

出版信息

Breast Cancer Res Treat. 2023 Jun;199(2):401-413. doi: 10.1007/s10549-023-06921-3. Epub 2023 Apr 3.

Abstract

BACKGROUND

The immune landscape of breast cancer (BC) in patients from Sub Saharan Africa is understudied. Our aims were to describe the distribution of Tumour Infiltrating Lymphocytes (TILs) within the intratumoural stroma (sTILs) and the leading/invasive edge stroma (LE-TILs), and to evaluate TILs across BC subtypes with established risk factors and clinical characteristics in Kenyan women.

METHODS

Visual quantification of sTILs and LE-TILs were performed on Haematoxylin and eosin -stained pathologically confirmed BC cases based on the International TIL working group guidelines. Tissue Microarrays were constructed and stained with immunohistochemistry (IHC) for CD3, CD4, CD8, CD68, CD20, and FOXP3. Linear and logistic regression models were used to assess associations between risk factors and tumour features with IHC markers and total TILs, after adjusting for other covariates.

RESULTS

A total of 226 invasive BC cases were included. Overall, LE-TIL (mean = 27.9, SD = 24.5) proportions were significantly higher than sTIL (mean = 13.5, SD = 15.8). Both sTILs and LE- TILs were predominantly composed of CD3, CD8, and CD68. We found higher TILs to be associated with high KI67/high grade and aggressive tumour subtypes, although these associations varied by TIL locations. Older age at menarche (≥ 15 vs. < 15 years) was associated with higher CD3 (OR: 2.06, 95%CI:1.26-3.37), but only for the intra-tumour stroma.

CONCLUSION

The TIL enrichment in more aggressive BCs is similar to previously published data in other populations. The distinct associations of sTIL/LE-TIL measures with most examined factors highlight the importance of spatial TIL evaluations in future studies.

摘要

背景

撒哈拉以南非洲地区乳腺癌(BC)患者的免疫景观研究较少。我们的目的是描述肿瘤内基质(sTILs)和主导/浸润边缘基质(LE-TILs)中肿瘤浸润淋巴细胞(TILs)的分布,并评估肯尼亚女性中具有既定风险因素和临床特征的 BC 亚型的 TILs。

方法

根据国际 TIL 工作组指南,对苏木精和伊红染色的病理证实的 BC 病例进行 sTILs 和 LE-TILs 的视觉量化。构建组织微阵列并用免疫组织化学(IHC)染色 CD3、CD4、CD8、CD68、CD20 和 FOXP3。在调整其他协变量后,使用线性和逻辑回归模型评估风险因素和肿瘤特征与 IHC 标志物和总 TILs 之间的关联。

结果

共纳入 226 例浸润性 BC 病例。总体而言,LE-TIL(平均=27.9,SD=24.5)比例明显高于 sTIL(平均=13.5,SD=15.8)。sTILs 和 LE-TILs 主要由 CD3、CD8 和 CD68 组成。我们发现较高的 TILs 与高 Ki67/高分级和侵袭性肿瘤亚型相关,尽管这些关联因 TIL 位置而异。初潮年龄较大(≥15 岁与<15 岁)与较高的 CD3(OR:2.06,95%CI:1.26-3.37)相关,但仅与肿瘤内基质相关。

结论

在更具侵袭性的 BC 中 TIL 富集与其他人群中先前发表的数据相似。sTIL/LE-TIL 测量与大多数检查因素的独特关联突出了在未来研究中进行空间 TIL 评估的重要性。

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