Background:Obesity is a risk factor of several types of cancer, including breast cancer. In this study, we aimed to histologically characterize the adipose tissue of the tumor microenvironment (TME) of triple-negative breast cancer (TNBC) in overweight/obese versus normal-weight patients.Methods:TNBC tissue sections from normal-weight (BMI<25) and overweight/obese patients (BMI≥25) were stained with antibodies against CD68, CD163, CD31, CD34, and vimentin. At the invasive tumor front, positive cells were counted in tumor adjacent adipose tissue (AT) and within cancer tissue (CT). Further, the size of the tumor-adjacent and distant mammary adipocytes was determined in perilipin stained sections. Expression of ANGPTL4, CD36 and FABP4, proteins involved in fatty acid metabolism, was analyzed in marginal tumor cells using an immune reactive score.Results:Overweight/obese TNBC patients had significantly larger adipocytes, higher numbers of CD163+ macrophages (BMI<25: 2.80 vs. BMI≥25: 10.45;p= 0.011) and lower numbers of CD31+ (BMI<25: 4.20 vs. BMI≥25: 2.40;p= 0.018) and CD34+ (BMI<25: 14.60 vs. BMI≥25: 5.20;p= 0.045) cells as markers of angiogenesis in the AT as well as a higher frequency of cancer-associated-fibroblast-like cells in the AT and CT (BMI<25: 7.60 vs. BMI≥25: 25.39 in total;p= 0.001). Moreover, expression of CD36 (BMI<25: 2.15 vs. BMI≥25: 2.60;p= 0.041) and ANGPTL4 (BMI<25: 6.00 vs. BMI≥25: 9.80;p= 0.026) was elevated in the TNBC cells of overweight/obese patients.Conclusions:Our data suggest BMI-related changes in the TME of overweight/obese TNBC patients, including hypertrophied adipocytes, reduced vascularization, more M2-like macrophages and CAF-like cells, and an increase in the expression of fatty acid metabolizing proteins in marginal tumor cells, all contributing to a more tumor-promoting, immunosuppressive environment.
背景：肥胖是包括乳腺癌在内的多种癌症的风险因素。本研究旨在从组织学角度比较超重/肥胖与正常体重患者三阴性乳腺癌（TNBC）肿瘤微环境（TME）中脂肪组织的特征差异。 方法：收集正常体重（BMI<25）与超重/肥胖（BMI≥25）TNBC患者的肿瘤组织切片，采用CD68、CD163、CD31、CD34及波形蛋白抗体进行染色。在肿瘤侵袭前沿，分别计数肿瘤邻近脂肪组织（AT）和癌组织（CT）内的阳性细胞数。此外，通过围脂滴蛋白染色切片测定肿瘤邻近及远端乳腺脂肪细胞的大小。采用免疫反应评分法分析边缘肿瘤细胞中脂肪酸代谢相关蛋白ANGPTL4、CD36和FABP4的表达水平。 结果：超重/肥胖TNBC患者的脂肪细胞显著增大，AT中CD163+巨噬细胞数量更高（BMI<25：2.80 vs. BMI≥25：10.45；p=0.011），而作为血管生成标志的CD31+（BMI<25：4.20 vs. BMI≥25：2.40；p=0.018）和CD34+细胞数量更低（BMI<25：14.60 vs. BMI≥25：5.20；p=0.045）。同时，AT与CT中癌症相关成纤维样细胞出现频率更高（总计：BMI<25：7.60 vs. BMI≥25：25.39；p=0.001）。此外，超重/肥胖患者TNBC细胞中CD36（BMI<25：2.15 vs. BMI≥25：2.60；p=0.041）和ANGPTL4表达升高（BMI<25：6.00 vs. BMI≥25：9.80；p=0.026）。 结论：本研究数据表明，超重/肥胖TNBC患者的TME存在与BMI相关的改变，包括脂肪细胞肥大、血管化减少、更多M2样巨噬细胞和CAF样细胞聚集，以及边缘肿瘤细胞脂肪酸代谢蛋白表达上调。这些变化共同构成了更具促肿瘤性和免疫抑制性的微环境。
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