基于 DNA 超分子水凝胶的保护性 NK 细胞储库用于增强三阴性乳腺癌治疗
Protective NK Cell Reservoir Based on DNA Supramolecular Hydrogel for Enhanced Triple-Negative Breast Cancer Therapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Tumor Microenvironment Modulation by Tumor-Associated Macrophages: Implications for Neoadjuvant Chemotherapy Response in Breast Cancer.
Tumor Microenvironment Modulation by Tumor-Associated Macrophages: Implications for Neoadjuvant Chemotherapy Response in Breast Cancer.
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本研究强调了 TAMs 动态在塑造 BC 中 NAC 反应的关键作用。值得注意的是,CD163+ TAMs 可能成为化疗耐药和反应机制中的关键参与者,突显了其作为乳腺癌治疗中生物标志物和治疗靶点的潜力。
肿瘤相关巨噬细胞(TAMs)是乳腺癌(BC)肿瘤微环境的重要组成部分,在调节肿瘤生长和侵袭中发挥重要作用。然而,TAMs在新辅助化疗(NAC)中的作用尚未完全阐明。因此,本研究旨在评估TAM亚型的功能,并探讨其在BC对NAC反应中的作用。
在138例BC患者队列中,通过IHC检测了NAC治疗前后肿瘤组织中TAMs的存在情况。使用CD68和CD163单克隆抗体进行IHC染色。阳性定义为间质和肿瘤细胞巢中TAMs染色>1%。NAC反应根据肿瘤大小变化和RCB指数进行评估。
NAC后,CD68+和CD163+ TAM在间质和肿瘤巢(TN)中均显著减少。间质中CD68+ TAM的中位数从5%显著降至1%(p < 0.005),而CD163+ TAM从20%显著降至5%(p < 0.001)。NAC后,间质中CD68+和CD163+ TAM的持续存在与较大的残留肿瘤大小密切相关(分别为p < 0.005和p < 0.001)。间质中CD163+ TAM水平的变化与RCB分级显著相关(p < 0.005)。NAC前,间质和TN中的CD163+ TAM与TILs显著相关;然而,NAC后未观察到与TILs的相关性。
Tumor-associated macrophages (TAMs) constitute an important part of the tumor microenvironment of breast cancer (BC), and they play an essential role in modulating tumor growth and invasion. However, the role of TAMs in neoadjuvant chemotherapy (NAC) has not been fully elucidated. Therefore, the aim of this study was to assess the function of TAM subtypes and investigate their role in the response to NAC in BC.
Presence of TAMs was examined immunohistochemically (IHC) in pre- and post- NAC treatment tumor tissue in a cohort of 138 BC patients. IHC staining with monoclonal antibodies for CD68 and CD163 were performed. Positivity was defined as staining > 1% TAMs in stroma and tumor cell nests. Response to NAC was evaluated according to tumor size change and Residual Cancer Burden (RCB) index.
CD68+ and CD163+ TAMs decreased significantly in both the stroma and tumor nests (TN) after NAC. The median CD68+ TAMs in the stroma decreased significantly from 5% to 1% (p < 0.005), while CD163+ TAMs showed a marked reduction from 20% to 5% (p < 0.001). Post-NAC, the persistence of CD68+ and CD163+ TAMs in the stroma was strongly correlated with larger residual tumor size (p < 0.005 and p < 0.001, respectively). Changes in CD163+ TAM levels in the stroma were significantly associated with RCB classes (p < 0.005). Pre-NAC, CD163+ TAMs in the stroma and TN showed a significant association with TILs; however, no correlations with TILs were observed post-NAC.
This study highlights the critical role of TAMs dynamics in shaping NAC response in BC. Notably, CD163+ TAMs may emerge as pivotal players in mechanisms of chemotherapy resistance and response, underscoring their potential as biomarkers and therapeutic targets in breast cancer treatment.
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