与新辅助化学免疫治疗对三阴性乳腺癌的差异反应相关的免疫因素
Robert J Seager1, Heidi Ko2, Sarabjot Pabla1
1Labcorp Oncology, Buffalo, NY 14263, USA.
Journal of personalized medicine
|May 25, 2024
概括
研究人员在瘤微环境中确定了免疫生物标志物,以预测早期三阴性乳腺癌 (TNBC) 的病理完整反应 (pCR). 这可以通过识别那些仅从化疗中受益的人来帮助患者免受免疫疗法的副作用.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 基因组学就是基因组学.
背景情况:
- KEYNOTE-522试验导致FDA批准了pembrolizumab与新辅助化疗用于高风险的早期三阴性乳腺癌 (TNBC).
- 作为一种免疫检查点抑制剂的 pembrolizumab 与免疫相关的不良事件 (irAEs) 有关.
- 识别生物标志物来预测单独对化疗的病理完整反应 (pCR),可以使患者免受不必要的免疫治疗.
研究的目的:
- 识别瘤微环境 (TME) 生物标志物,这些生物标志物可以预测单独使用新辅助化疗治疗的TNBC患者的pCR.
- 为了区分那些可能受益于单独化疗与 pembrolizumab 联合治疗的患者.
主要方法:
- 使用RNA-seq对22名TNBC患者FFPE瘤样本中的395个免疫基因进行全面的免疫分析.
- 患者被分为两组:单独接受新辅助化疗 (NAC) 和接受新辅助化疗加 pembrolizumab (NAC+I).
- 进行了差异基因表达分析,以将免疫基因表达与pCR相关联.
主要成果:
- 在NAC组中,IL12B和IL13基因表达与pCR显著相关.
- 在NAC+I组中,LCK和TP63基因表达与pCR显著相关.
- 在两组中获得pCR的患者表现出瘤炎症的增加;pCR的NAC+I组具有较高的细胞增殖和PD-L1表达,而PCR的NAC组具有较低的癌症丸抗原表达.
结论:
- 在TNBC中,TME中的特定免疫因素可能会预测单独化疗的pCR.
- 识别这些生物标志物可以使治疗减缓,使患者免受免疫疗法及其相关的irAEs.
- 对这些生物标志物的进一步研究可以为早期TNBC个性化新辅助治疗策略.
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