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.
过继性自然杀伤(NK)细胞疗法是治疗三阴性乳腺癌的一种有前景的策略,但其疗效往往受到瘤内持久性差以及在免疫抑制性肿瘤微环境中功能耗竭的限制。
英文原题:Tumor P70S6K hyperactivation is inversely associated with tumor-infiltrating lymphocytes in triple-negative breast cancer.
Tumor P70S6K hyperactivation is inversely associated with tumor-infiltrating lymphocytes in triple-negative breast cancer.
sTIL浸润和淋巴细胞谱在TNBC肿瘤中P70S6K过度激活的背景下存在差异。
三阴性乳腺癌(TNBC)具有高度异质性和相对缺乏可用靶向疗法的特点。为了寻找针对不同TNBC患者的治疗策略,已采用多种方法对TNBC进行聚类分析,包括近期的免疫和磷酸化蛋白质组学模式。基于70-kDa核糖体蛋白S6激酶(P70S6K)-TNBC聚类,本研究探索了TNBC肿瘤中的免疫特征。
在人TNBC肿瘤样本中评估了基质TIL(肿瘤浸润淋巴细胞)(sTILs)。此外,在组织微阵列(TMA)切片中进行了CD8、CD4、Foxp3和CD20的免疫组化染色。
组织学分析显示,在高磷酸化 P70S6K(p-P70S6K)肿瘤中,sTILs、CD20 + 细胞以及 CD8 + /CD4 + 比值降低。此外,p-P70S6K 评分与 CD4 + 和 Foxp3 + T 细胞直接相关,而与 CD8 + /CD4 + 和 CD8 + /Foxp3 + 比值呈负相关。
PURPOSE: Triple-negative breast cancer (TNBC) is characterized by large heterogeneity and relative lack of available targeted therapies. To find therapeutic strategies for distinct patients with TNBC, several approaches have been used for TNBC clustering, including recently immune and phosphoproteomic patterns. Based on 70-kDa ribosomal protein S6 kinase (P70S6K)-TNBC clustering, the current study explores the immune profiling in TNBC tumors. METHODS: Stromal tumor-infiltrating lymphocytes (sTILs) were evaluated in human TNBC tumor samples. Furthermore, immunohistochemistry staining for CD8, CD4, Foxp3, and CD20 was performed in tissue microarrays (TMA) sections. RESULTS: Histological analysis showed decreased sTILs, CD20 + cells, and CD8 + /CD4 + ratio in high phosphorylated P70S6K (p-P70S6K) tumors. Moreover, p-P70S6K score was directly correlated with CD4 + and Foxp3 + T cells, while it was inversely correlated with CD8 + /CD4 + and CD8 + /Foxp3 + ratios. CONCLUSION: sTIL infiltration and lymphocyte profiling vary in the context of hyperactivation of P70S6K in TNBC tumors.
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