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:Immune environment of high-TIL breast cancer: triple negative and hormone receptor positive HER2 negative.
Immune environment of high-TIL breast cancer: triple negative and hormone receptor positive HER2 negative.
高 TIL 的三阴性乳腺癌(TNBC)与 HR⁺HER2⁻ 乳腺癌(BC)中 IC 的组成和空间分布存在显著差异,并受 PD-L1 状态影响。
本研究考察高TIL(≥60%)病例中,三阴性乳腺癌(TNBC)与激素受体阳性、HER2阴性乳腺癌(HR+/HER2-BC)的免疫细胞(IC)组成和空间分布差异,并重点分析PD-L1状态。研究使用多重免疫荧光,对18例TNBC和14例HR+/HER2-BC切除肿瘤组织中的IC类型(CD20、CD8、CD4、FOXP3)及其空间相互作用进行分析。与HR+/HER2-BC相比,TNBC具有独特的IC组成,其CD8+ IC比例较高(间质:27%对17%,p<0.001;肿瘤:54%对31%,p<0.001),间质CD4+FOXP3+ IC比例也更高(3.9%对3.0%,p=0.036)。值得注意的是,与HR+/HER2-BC相比,PD-L1阳性TNBC病例间质区CD4+FOXP3+ IC浸润更密集(146.4±67.1/mm²对114.3±146.9/mm²,p=0.036),且免疫细胞在肿瘤细胞(TC)附近明显聚集。两种肿瘤亚型的IC组成均随PD-L1状态而异。总之,高TIL TNBC与HR+/HER2-BC的免疫细胞组成及空间分布存在显著差异,并受到PD-L1状态影响。
This study explores differences in immune cell (IC) composition and spatial distribution between triple-negative breast cancer (TNBC) and hormone receptor-positive, HER2-negative breast cancer (HR + HER2-BC) in high-TIL ( 60%) cases, focusing on PD-L1 status. Using multiplex immunofluorescence on resected tumor tissues from 18 TNBC and 14 HR + HER2-BC cases, we analyzed IC types (CD20, CD8, CD4, FOXP3) and their spatial interactions. TNBC showed a unique IC composition characterized by a higher proportion of CD8 + IC (stroma: 27% vs 17%, p < 0.001; tumor: 54% vs 31%, p < 0.001) and CD4 + FOXP3 + IC (stroma: 3.9% vs 3.0%, p = 0.036), compared to HR + HER2-BC. Notably, PD-L1 positive TNBC cases demonstrated denser infiltration CD4 + FOXP3 + IC in the stromal region compared to HR + HER2-BC (146.4 67.1/mm 2 vs 114.3 146.9/mm 2 , p = 0.036), along with pronounced IC clustering near TC. Both tumor subtypes displayed varied IC compositions based on PD-L1 status. In conclusion, IC composition and spatial distribution in high-TIL TNBC and HR + HER2-BC significantly differ, influenced by PD-L1 status.
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