Goda Noriko, Nakashima Chika, Nagamine Ichiro, Otagaki Sunao
Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
Department of Surgery, Hiroshima Kyoritsu Hospital, 2-20-20 Nakasu, Asaminami-ku, Hiroshima 731-0121, Japan.
Cancers (Basel). 2022 Apr 25;14(9):2138. doi: 10.3390/cancers14092138.
Triple-negative breast cancer (TNBC) is characterized by an active immune response. We evaluated intratumoral interrelation between FOXP3+ tumor-infiltrating lymphocytes and other cytokines in TNBC. Network analysis refined cytokines significantly correlate with FOPX3 in TNBC. Information on the treatment response and prognosis of patients, and survival data from the TGCA and METABRIC databases were analyzed according to refined cytokines. Interleukin (IL)-33 was significantly expressed by TNBC cell lines compared to luminal cell lines (log2 fold change: 5.31, p < 0.001) and IL-33 and TGFB2 showed a strong correlation with FOXP3 in the TNBC cell line. Immunohistochemistry demonstrated that the IL-33 high group was a significant predictor of complete response of neoadjuvant chemotherapy (odds ratio (OR) 4.12, p < 0.05) and favorable survival compared to the IL-33 low group (OR 6.48, p < 0.05) in TNBC. Survival data from TGCA and METABRIC revealed that FOXP3 was a significantly favorable marker in the IL-33 high group compared to the low IL-33 low group (hazard ratio (HR) 2.1, p = 0.02), and the IL-33 high/TGFB2 high subgroup showed significant favorable prognosis in the FOXP3 high group compared to the FOPX3 low group in TNBC (HR 3.5, p = 0.01). IL-33 and TGFB2 were key cytokines of intratumoral interrelation among FOXP3 in TNBC.
三阴性乳腺癌（TNBC）的特征是具有活跃的免疫反应。我们评估了TNBC中FOXP3 +肿瘤浸润淋巴细胞与其他细胞因子之间的瘤内相互关系。网络分析显示，TNBC中与FOPX3显著相关的细胞因子得到了优化。根据优化后的细胞因子，分析了患者的治疗反应和预后信息以及来自TGCA和METABRIC数据库的生存数据。与管腔细胞系相比，TNBC细胞系中白细胞介素（IL）-33的表达显著升高（log2倍数变化：5.31，p <0.001），并且在TNBC细胞系中IL-33和TGFB2与FOXP3显示出强相关性。免疫组织化学表明，在TNBC中，IL-33高表达组是新辅助化疗完全缓解的显著预测指标（优势比（OR）4.12，p <0.05），与IL-33低表达组相比，生存情况良好（OR 6.48，p <0.05）。来自TGCA和METABRIC的生存数据显示，与IL-33低表达组相比，FOXP3在IL-33高表达组中是一个显著有利的标志物（风险比（HR）2.1，p = 0.02），并且在TNBC中，与FOXP3低表达组相比，IL-33高/TGFB2高亚组在FOXP3高表达组中显示出显著良好的预后（HR 3.5，p = 0.01）。IL-33和TGFB2是TNBC中FOXP3瘤内相互关系的关键细胞因子。
