The Cancer Center, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, China.
Biomolecules. 2023 Feb 22;13(3):415. doi: 10.3390/biom13030415.
In the past few years, immune checkpoint blockade (ICB) therapy has emerged as a breakthrough treatment for cancers and has demonstrated inspiring effects in tumor patients with Epstein-Barr virus (EBV) infection. To allow more patients to benefit from immunotherapy, exploring novel biomarkers based on EBV-related tumors and immunotherapy cohorts was pursued in the present study. The essential biomarkers that may enhance antitumor immunity across EBV-related tumors were identified using the large-scale transcriptomic profiles of EBV-associated tumors and tumor immunotherapy cohorts. The clinical significance of vital genes was evaluated in multiple tumor immunotherapy cohorts. Moreover, the potential function of essential genes in immunotherapy was explored via bioinformatic analyses and verified by qRT-PCR, Western blot analysis, CCK8 assay and flow cytometry. Apolipoprotein L6 (APOL6) was considered the essential biomarker for enhancing antitumor immunity across EBV-positive tumors. The upregulation of APOL6 was correlated with increased response rates and prolonged survival in multiple tumor immunotherapy cohorts. Bioinformatic analyses suggested that APOL6 may enhance tumor immunotherapy by inducing immunogenic cell death. Pancreatic cancer cells transfected with APOL6 overexpression plasmid underwent apoptosis, necroptosis, and pyroptosis with immunogenic features. The biomarker upregulated in EBV-related tumors could further elucidate the drivers of immunotherapy response. The upregulation of APOL6 could improve immunotherapy by triggering immunogenic cell death, thus offering a new target to optimize cancer immunotherapy.
在过去的几年中，免疫检查点阻断 (ICB) 疗法已成为癌症治疗的突破，并在 EBV 感染的肿瘤患者中显示出令人鼓舞的效果。为了让更多的患者受益于免疫疗法，本研究旨在探索基于 EBV 相关肿瘤和免疫治疗队列的新型生物标志物。通过 EBV 相关肿瘤和肿瘤免疫治疗队列的大规模转录组谱，确定了可能增强 EBV 相关肿瘤抗肿瘤免疫的基本生物标志物。在多个肿瘤免疫治疗队列中评估了关键基因的临床意义。此外，通过生物信息学分析探讨了关键基因在免疫治疗中的潜在功能，并通过 qRT-PCR、Western blot 分析、CCK8 测定和流式细胞术进行了验证。载脂蛋白 L6 (APOL6) 被认为是增强 EBV 阳性肿瘤抗肿瘤免疫的基本生物标志物。APOL6 的上调与多个肿瘤免疫治疗队列中反应率的提高和生存时间的延长相关。生物信息学分析表明，APOL6 可能通过诱导免疫原性细胞死亡来增强肿瘤免疫治疗。转染了 APOL6 过表达质粒的胰腺癌细胞发生了具有免疫原性的凋亡、坏死和焦亡。在 EBV 相关肿瘤中上调的生物标志物可以进一步阐明免疫治疗反应的驱动因素。APOL6 的上调可以通过触发免疫原性细胞死亡来改善免疫治疗，从而为优化癌症免疫治疗提供了一个新的靶点。
