表达MIF的瘤细胞在食道状细胞癌中调解免疫治疗抵抗
Jing Song1, Xiaomei Song2, Yue Xie1
1Pediatric Research Institute, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Cognitive Development and Learning and Memory Disorders, National Clinical Research Center for Child Health and Disorders, Children's Hospital of Chongqing Medical University, No. 136 Zhongshan 2nd Road, Yuzhong District, 400014, Chongqing, China.
Theranostics
|December 8, 2025
概括
巨细胞迁移抑制因子 (MIF) 由生殖中心 (GC) 的瘤细胞产生,预测食道状细胞癌 (ESCC) 的免疫疗法耐药性. 这种MIF破坏了B细胞免疫力,导致治疗失败.
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:
- 免疫疗法对于食道状细胞癌 (ESCC) 治疗至关重要.
- 在ESCC免疫疗法中治疗失败需要了解潜在的抵抗机制.
研究的目的:
- 在疾病进展和免疫治疗反应期间,全面分析ESCC中的瘤微环境 (TME).
- 确定驱动ESCC免疫疗法耐药性的分子机制.
主要方法:
- 从192名ESCC患者的大规模单细胞RNA测序 (scRNA-seq) 数据的综合分析.
- 在配对的治疗前和治疗后组织上高分辨率的空间转录组学 (stRNA-seq).
- 多重复合免疫组织化学验证细胞间交叉模式.
主要成果:
- 在ESCC进展过程中减少B系细胞;在免疫疗法耐药患者中增强.
- 免疫疗法耐药性与ESCC细胞的一个子集中的胆固醇生物合成有关.
- 胆固醇生物合成瘤细胞和生殖中心 (GC) B细胞之间的交叉声被确定为一种抵抗机制.
- 在与胆固醇生物合成相关的ESCC细胞中增加的巨细胞迁移抑制因子 (MIF) 通过MIF-CXCR4相互作用破坏B细胞免疫力.
结论:
- 在生殖中心 (GCs) 内的巨细胞迁移抑制因子 (MIF) 阳性瘤细胞可以作为ESCC免疫疗法耐药性的预测生物标志物.
- 针对MIF-CXCR4相互作用可能有可能克服ESCC的免疫疗法耐药性.
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