下一代肿瘤不可知靶点即将出现
Next-generation tumor-agnostic targets on the horizon.
肿瘤不可知药物开发将肿瘤学重新聚焦于共享的分子依赖性而非组织来源,从而能够针对跨肿瘤的罕见可操作驱动因素进行高效开发。
英文原题:Characterization of the Immune Microenvironment in Inflammatory Breast Cancer Using Multiplex Immunofluorescence.
Characterization of the Immune Microenvironment in Inflammatory Breast Cancer Using Multiplex Immunofluorescence.
这些结果揭示了IBC中免疫细胞亚型分布的复杂独特模式,并为详细描述控制IBC免疫景观形成的分子通路及免疫治疗潜力提供了重要基础。
炎性乳腺癌(IBC)是一种侵袭性乳腺癌,其免疫微环境特征尚不明确。
我们使用了一个五色多重免疫荧光panel,包括CD68、CD4、CD8、CD20和FOXP3,对93例未经治疗的IBC样本进行免疫微环境分析。
低级别肿瘤的特征是CD4+细胞减少,但FOXP3+细胞积聚增加。CD20+细胞增加与新辅助化疗反应更好相关,CD4+细胞浸润增加与更好的总生存相关。配对分析显示,ER+和三阴性乳腺癌均以CD20+细胞与CD68+和CD4+细胞共同浸润为特征,而CD8+和CD68+细胞的共同浸润仅在HER2+ IBC中观察到。CD20+、CD8+、CD4+和FOXP3+细胞的共同浸润,以及CD68+与FOXP3+细胞的共存与更好的治疗反应相关,而耐药肿瘤的特征是CD4+、CD8+、FOXP3+和CD68+细胞的共同积聚以及CD68+和CD20+细胞的共同表达。在Cox回归模型中,治疗反应是与患者生存改善相关的最显著因素。
INTRODUCTION: Inflammatory breast cancer (IBC) is an aggressive form of breast cancer with a poorly characterized immune microenvironment. METHODS: We used a five-colour multiplex immunofluorescence panel, including CD68, CD4, CD8, CD20, and FOXP3 for immune microenvironment profiling in 93 treatment-naïve IBC samples. RESULTS: Lower grade tumours were characterized by decreased CD4+ cells but increased accumulation of FOXP3+ cells. Increased CD20+ cells correlated with better response to neoadjuvant chemotherapy and increased CD4+ cells infiltration correlated with better overall survival. Pairwise analysis revealed that both ER+ and triple-negative breast cancer were characterized by co-infiltration of CD20 + cells with CD68+ and CD4+ cells, whereas co-infiltration of CD8+ and CD68+ cells was only observed in HER2+ IBC. Co-infiltration of CD20+, CD8+, CD4+, and FOXP3+ cells, and co-existence of CD68+ with FOXP3+ cells correlated with better therapeutic responses, while resistant tumours were characterized by co-accumulation of CD4+, CD8+, FOXP3+, and CD68+ cells and co-expression of CD68+ and CD20+ cells. In a Cox regression model, response to therapy was the most significant factor associated with improved patient survival. CONCLUSION: Those results reveal a complex unique pattern of distribution of immune cell subtypes in IBC and provide an important basis for detailed characterization of molecular pathways that govern the formation of IBC immune landscape and potential for immunotherapy.
MEMBER ACCOUNT
登录成功会直接打开下一页。