工程化益生菌用于肿瘤靶向联合化学免疫治疗
Engineered probiotics for tumor-targeted combination chemoimmunotherapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
泛癌分析确定 ODF2 作为免疫治疗的双重预后和预测生物标志物
英文原题：Pan-cancer analysis identifies ODF2 as a dual prognostic and predictive biomarker for immunotherapy.
查看英文原题
Pan-cancer analysis identifies ODF2 as a dual prognostic and predictive biomarker for immunotherapy.
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研究概要
ODF2 与免疫抑制性 TME 密切相关，可作为 ICB 疗效的预测生物标志物。这些发现并未将其确证为普适靶点，而是为将 ODF2 作为下一代多肽疫苗和过继性 T 细胞疗法以克服 ICB 耐药的潜在候选靶点开展研究提供了理论依据。
研究思路结论见上方概要
背景
将免疫学“冷”肿瘤转化为炎症性“热”肿瘤仍是癌症免疫治疗的主要障碍。癌症-睾丸抗原（CTAs）是下一代治疗性癌症疫苗和过继细胞疗法极具前景的靶点。然而，新兴CTA Outer Dense Fiber 2（ODF2）在人类恶性肿瘤中的系统性免疫基因组景观及预后意义仍 largely 未被探索。本研究全面解码ODF2的泛癌免疫学和预后特征，以评估其广谱临床实用性。
方法
对来自TCGA、GTEx和HPA数据库的多组学及临床数据进行分析，以评估ODF2的预后价值。进行基因集富集分析（GSEA）以识别相关的生物学通路。使用多种解卷积算法评估ODF2表达、免疫细胞浸润和免疫检查点之间的相关性。利用来自BEST数据库的独立临床队列评估ODF2对免疫检查点阻断（ICB）治疗的预测价值。
结果
ODF2在多种实体瘤中显著上调，并与不良临床结局相关。GSEA显示，ODF2高表达在细胞周期和致癌通路上强烈富集。此外，ODF2表达与免疫抑制性细胞群体和主要抑制性免疫检查点呈正相关，而与浸润性CD8+ T细胞呈负相关。ROC分析表明，ODF2表达能可靠预测不同临床队列中对anti-PD-1和anti-CTLA-4治疗的临床反应性。
展开英文摘要原文
BACKGROUND
Transforming immunologically "cold" tumors into inflamed "hot" remains a primary hurdle in cancer immunotherapy. Cancer-testis antigens (CTAs) represent highly promising targets for next-generation therapeutic cancer vaccines and adoptive cell therapies. However, the systemic immunogenomic landscape and prognostic significance of Outer Dense Fiber 2 (ODF2), an emerging CTA, across human malignancies remain largely unexplored. This study comprehensively decodes the pan-cancer immunological and prognostic characteristics of ODF2 to evaluate its broad-spectrum clinical utility.
METHODS
Multi-omics and clinical data from the TCGA, GTEx, and HPA databases were analyzed to assess the prognostic value of ODF2. Gene Set Enrichment Analysis (GSEA) was performed to identify associated biological pathways. The correlation between ODF2 expression, immune cell infiltration, and immune checkpoints was evaluated using multiple deconvolution algorithms. The predictive value of ODF2 for immune checkpoint blockade (ICB) therapy was assessed using independent clinical cohorts from the BEST database.
RESULTS
ODF2 is significantly upregulated across multiple solid tumors and correlates with poor clinical outcomes. GSEA revealed that high ODF2 expression is strongly enriched in cell cycle and oncogenic pathways. Furthermore, ODF2 expression exhibits positive correlation with immunosuppressive cell populations and major inhibitory immune checkpoints, while inversely correlating with infiltrating CD8 + T cells. ROC analyses demonstrated that ODF2 expression reliably predicts clinical responsiveness to anti-PD-1 and anti-CTLA-4 therapies in diverse clinical cohorts.
CONCLUSIONS
ODF2 is strongly associated with an immunosuppressive TME and serves as a predictive biomarker for ICB efficacy. Rather than definitively validating it as a universal target, these findings provide a theoretical rationale for investigating ODF2 as a potential candidate for next-generation peptide vaccines and adoptive T-cell therapies to overcome ICB resistance.
论文信息
- 作者
- Guo W、Ran L、Shao X、Tian Y、Shi R
- 第一作者单位
- Department of Basic Medical Sciences, Luohe Medical College, Luohe, 462000, China.China
- 通讯作者单位
- Department of Basic Medical Sciences, Luohe Medical College, Luohe, 462000, China. ranranpeptide@163.com.China
- 期刊
- Discover oncology2026 Jul 29
- 原文标识
- PubMed 42690554 · DOI 10.1007/s12672-026-05694-7