CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:ITM2A as a potential prognostic marker for triple-negative breast cancer.
ITM2A as a potential prognostic marker for triple-negative breast cancer.
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乳腺癌的不同亚型给精准治疗带来了巨大挑战,尤其是三阴性乳腺癌(TNBC),因其缺乏有效的治疗靶点且对化疗高度耐药。在本研究中,跨膜蛋白 ITM2A 被系统鉴定为 TNBC 的一种新型预后生物标志物和潜在治疗靶点。差异表达谱分析显示,ITM2A 在 TNBC 组织中显著低表达。
此外,ITM2A 低表达患者的 OS、RFS 和 DMFS 均较差。联合多组学分析揭示,ITM2A 低表达与免疫抑制性微环境特征显著相关。
值得注意的是,ITM2A 高表达组在抗 PD-L1 治疗(AUC=0.982)和 CAR-T 治疗(AUC=0.827)中表现出显著的临床获益。基因本体 功能注释和 KEGG 通路富集分析表明,ITM2A 可能通过调控铜离子代谢重编程和免疫检查点网络来协调抗肿瘤免疫应答。药物基因组学分析进一步证实,ITM2A 的表达水平与依托泊苷的敏感性呈负相关。通过建立 ITM2A 的“免疫代谢-治疗反应”调控轴,本研究希望为 TNBC 的靶向治疗和免疫治疗的精准分层提供创新的理论依据。
Different subtypes of breast cancer pose great challenges for precision therapy, especially triple-negative breast cancer (TNBC), because it lacks effective therapeutic targets and is highly resistant to chemotherapy. In this study, the transmembrane protein ITM2A was systematically identified as a novel prognostic biomarker and potential therapeutic target for TNBC. ITM2A was found to be significantly under expressed in TNBC tissues, as revealed by differential expression profiling.
Furthermore, patients exhibiting low ITM2A expression demonstrated worse overall survival (OS), recurrence-free survival (RFS), and distant metastasis-free survival (DMFS). A combined multi-omics analysis revealed a significant association between low ITM2A expression and immunosuppressive microenvironmental features. It is noteworthy that the ITM2A high-expression group exhibited substantial clinical benefits in anti-PD-L1 treatment (AUC=0. 982) and CAR-T treatment (AUC=0. 827).
Gene Ontology functional annotation and KEGG pathway enrichment analysis indicated that ITM2A may coordinate anti-tumor immune responses by regulating copper ion metabolic reprogramming and immune checkpoint networks. Pharmacogenomic analysis further confirmed that the expression level of ITM2A was negatively correlated with the sensitivity of etoposide.
By establishing the 'immunometabolism-therapeutic response' regulatory axis of ITM2A, this study hopes to provide an innovative theoretical basis for the targeted treatment of TNBC and the precise stratification of immunotherapy.
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