γδ T 细胞调节小细胞肺癌中的抗肿瘤免疫
γδ T cells modulate anti-tumor immunity in small cell lung cancer.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
默克尔细胞癌免疫检查点抑制剂耐药的决定因素：叙述性综述
英文原题：Determinants of Resistance to Immune Checkpoint Inhibitors in Merkel Cell Carcinoma: A Narrative Review.
查看英文原题
Determinants of Resistance to Immune Checkpoint Inhibitors in Merkel Cell Carcinoma: A Narrative Review.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
研究概要
理解病毒状态、基因组负荷与免疫景观之间的相互作用对于克服 ICI 耐药至关重要。合理的联合策略，特别是 ICI 联合放疗或表观遗传调节剂以恢复 MHC-I 表达，为改善耐药疾病患者的结局提供了途径。
研究思路结论见上方概要
背景
Merkel细胞癌（MCC）是一种侵袭性神经内分泌皮肤恶性肿瘤，常与Merkel细胞多瘤病毒（MCPyV）或紫外线（UV）诱变相关。尽管靶向PD-1/PD-L1轴的免疫检查点抑制剂（ICIs）可实现50-60%的缓解率，但原发性和获得性耐药仍是重大挑战。本综述旨在综合当前关于MCC中ICI耐药决定因素的证据，以改善患者分层和治疗策略。
方法
通过使用SciSpace、Google Scholar和PubMed数据库，对学术文献进行了全面的叙述性回顾。分析了聚焦于MCC发病机制、免疫治疗临床试验、肿瘤微环境（TME）特征分析以及ICI耐药分子机制的研究。整合了29篇同行评审来源，以提供关于耐药性的多层次视角。
结果
MCC 中对 ICI 的耐药是多因素的，由 TME 异质性、MHC-I 下调、T 细胞耗竭以及病毒状态依赖的免疫识别所驱动。缺乏预先存在的组织驻留 CD8+ 和 γδ T 细胞回路的“冷”肿瘤易发生治疗失败。此外，肿瘤细胞可塑性——在神经上皮样和间充质样状态之间转换——主动塑造免疫逃逸。新兴生物标志物如循环肿瘤 DNA（ctDNA）和复合基因表达特征显示出前景，但需要前瞻性验证。
展开英文摘要原文
MATERIALS AND METHODS
A comprehensive narrative review of scholarly literature was performed using SciSpace, Google Scholar, and PubMed databases. Studies focused on MCC pathogenesis, immunotherapy clinical trials, tumor microenvironment (TME) profiling, and molecular mechanisms of ICI resistance were analyzed. A total of 29 peer-reviewed sources were integrated to provide a multi-layered perspective on resistance.
RESULTS
Resistance to ICIs in MCC is multifactorial, driven by TME heterogeneity, MHC-I down-regulation, T-cell exhaustion, and viral status-dependent immune recognition. "Cold" tumors lacking preexisting tissue-resident CD8+ and γδ T-cell circuits are predisposed to failure. Furthermore, tumor cell plasticity - shifting between neuroepithelial and mesenchymal-like states - actively shapes immune evasion. Emerging biomarkers such as circulating tumor DNA (ctDNA) and composite gene expression signatures show promise but require prospective validation.
CONCLUSION
Understanding the interplay between viral status, genomic burden, and the immune landscape is essential for overcoming ICI resistance. Rational combination strategies, particularly ICI plus radiation or epigenetic modulators to restore MHC-I expression, offer pathways to improve outcomes in resistant disease.
论文信息
- 作者
- Popp R、Gabriel EM
- 单位
- University of Florida College of Medicine, Gainesville, FL, U.S.A.; reedpopp@ufl.edu.United States
- 文献类型
- 综述
- 期刊
- Anticancer research2026 Jul
- 原文标识
- PubMed 42373245 · DOI 10.21873/anticanres.18223