Alterations in the Immune Cell Composition in Premalignant Breast Tissue that Precede Breast Cancer Development
Alterations in the Immune Cell Composition in Premalignant Breast Tissue that Precede Breast Cancer Development
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DOI：
10.1158/1078-0432.ccr-16-2026
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发表时间：
2017-07-15
影响因子：
11.5
通讯作者：
Visscher, Daniel W.
中科院分区：
文献类型：
--
作者：
Degnim, Amy C.;Hoskin, Tanya L.;Visscher, Daniel W.
目的：免疫系统在乳腺癌发生的最早阶段的作用知之甚少。我们研究了来自正常供体和良性乳腺疾病（BBD）妇女的乳腺组织之间免疫细胞类型的定量差异。来自治愈组织库（KTB）的科门和来自马约诊所（罗切斯特，MN）诊断为BBD的妇女，这些妇女随后发展成癌症（BBD病例）或保持无癌症（BBD对照）。对连续组织切片进行免疫染色，并对CD 4（+）T细胞、CD 8（+）T细胞、CD 20（+）B细胞和CD 68（+）巨噬细胞的每平方毫米细胞数进行数字定量，并对CD 11 c的阳性像素测量进行定量结果：在94例年龄匹配的三胞胎中，与KTB正常人相比，BBD小叶显示出更高密度的CD 8（+）T细胞、CD 11 c（+）树突状细胞、CD 20（+）B细胞和CD 68（+）巨噬细胞。与BBD对照组相比，BBD病例的CD 20（+）细胞密度较低（P = 0.04）。近42%的BBD病例在评估的小叶中没有CD 20（+）B细胞，而BBD对照组为28%（P = 0.02）。CD 20（+）细胞的存在与所有小叶的情况下，显示了调整后的OR为5.7（95%置信区间，1.4-23.1）为随后的乳腺癌risk.Conclusions：在BBD组织中，先天性和适应性免疫效应物的浸润升高提示免疫原性微环境。晚期乳腺癌患者的B细胞浸润减少表明B细胞在预防疾病进展中的作用，并作为乳腺癌风险的可能生物标志物。(C)2017年AACR。
Purpose: Little is known about the role of the immune system in the earliest stages of breast carcinogenesis. We studied quantitative differences in immune cell types between breast tissues from normal donors and those from women with benign breast disease (BBD).Experimental Design: A breast tissue matched case-control study was created from donors to the Susan G. Komen for the Cure Tissue Bank (KTB) and from women diagnosed with BBD at Mayo Clinic (Rochester, MN) who either subsequently developed cancer (BBD cases) or remained cancer-free (BBD controls). Serial tissue sections underwent immunostaining and digital quantification of cell number per mm2 for CD4(+) T cells, CD8(+) T cells, CD20(+) B cells, and CD68(+) macrophages and quantification of positive pixel measure for CD11c (dendritic cells).Results: In 94 age-matched triplets, BBD lobules showed greater densities of CD8(+) T cells, CD11c(+) dendritic cells, CD20(+) B cells, and CD68(+) macrophages compared with KTB normals. Relative to BBD controls, BBD cases had lower CD20(+) cell density (P = 0.04). Nearly 42% of BBD cases had no CD20(+) B cells in evaluated lobules compared with 28% of BBD controls (P = 0.02). The absence of CD20(+) cells versus the presence in all lobules showed an adjusted OR of 5.7 (95% confidence interval, 1.4-23.1) for subsequent breast cancer risk.Conclusions: Elevated infiltration of both innate and adaptive immune effectors in BBD tissues suggests an immunogenic microenvironment. The reduced B-cell infiltration in women with later breast cancer suggests a role for B cells in preventing disease progression and as a possible biomarker for breast cancer risk. (C) 2017 AACR.