在新辅助化疗驱动的免疫抑制瘤微环境中,克劳丁18.2-阳性胃癌特异性变化
Chikanori Tsutsumi1, Kenoki Ohuchida2,3, Yutaka Yamada4
1Department of Surgery and Oncology, Graduate School of Medical Sciences; Kyushu University, Fukuoka, Japan.
British journal of cancer
|March 25, 2025
概括
化疗改变了Claudin 18.2阳性胃癌的瘤微环境,增加了像Tregs和TAMs这样的免疫抑制细胞. 这些变化,包括改变的NK细胞功能,是CLDN18.2-阳性瘤的特征.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 癌症生物学 癌症生物学
背景情况:
- 克劳丁18异型2 (CLDN18.2) 是胃癌 (GC) 的治疗点.
- 在CLDN18.2-阳性GC中,结合化疗与抗CLDN18.2抗体的疗效有限.
- 在CLDN18.2-阳性GC中,化疗诱导的瘤微环境 (TME) 变化尚未得到充分理解.
研究的目的:
- 研究CLDN18.2-阳性GC中的化疗驱动的TME修饰.
- 评估化疗对免疫细胞群的影响及其在TME内的相互作用.
主要方法:
- 使用单细胞RNA测序和多重免疫光学分析37个GC样本 (11个CLDN18.2-阳性).
- 在CLDN18.2-阳性GC中评估化疗诱导的TME变化.
主要成果:
- 在CLDN18.2-阳性GC中,化疗治疗导致细胞毒性自然杀手 (NK) 细胞ADCC相关基因表达的降低.
- 在化疗后,调节性T细胞 (Tregs) 和瘤相关巨细胞 (TAMs) 中增加了TGFB1的丰度和表达.
- 化疗诱导的TME变化,包括改变的细胞信号传递 (CCL5-CCR5,TGFB1-TGFBR),是特定于CLDN18.2-阳性的GC.
结论:
- 化疗诱导了CLDN18.2-阳性GC中的免疫抑制TME修饰.
- 这些发现突出了TME变化作为潜在的机制限制组合治疗的疗效.
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