背景:使用免疫检查点抑制剂(ICI)的免疫治疗彻底改变了癌症治疗。然而,抑制性T细胞受体如PD-1的治疗靶向不仅引发广泛的抗肿瘤免疫反应,还会造成严重的不良影响。理想的未来分层免疫疗法将仅干扰癌症特异性细胞表面受体。
方法:为了确定这类候选人,我们通过流式细胞术分析了NCI-60肿瘤细胞组的表面受体。将所得的表面受体表达数据整合到蛋白质组和转录组NCI-60数据集中,应用复杂的多组学多惯性分析(MCIA)。这使我们能够识别皮肤的表面轮廓,大脑,结肠,肾,以及骨髓来源的细胞系和结肠癌和肾癌的癌症实体特异性细胞表面受体生物标志物。
结果:对于结肠癌,鉴定的生物标志物是CD15、CD104、CD324、CD326、CD49f、对于肾癌,CD24、CD26、CD106(VCAM1)、EGFR,SSEA-3(B3GALT5),SSEA-4(TMCC1),TIM1(HAVCR1),和TRA-1-60R(PODXL)。进一步的数据挖掘表明,CD106(VCAM1)尤其是用于治疗肾癌的有希望的新型免疫治疗靶标。
结论:总而言之,我们对NCI-60组的创新性多组学分析为揭示表面受体提供了非常有价值的资源,这些受体可在癌症免疫治疗的背景下进一步用于诊断和治疗目的.
BACKGROUND: Immunotherapy with immune checkpoint inhibitors (ICI) has revolutionized cancer therapy. However, therapeutic targeting of inhibitory T cell receptors such as PD-1 not only initiates a broad immune response against tumors, but also causes severe adverse effects. An ideal future stratified immunotherapy would interfere with cancer-specific cell surface receptors only.
METHODS: To identify such candidates, we profiled the surface receptors of the NCI-60 tumor cell panel via flow cytometry. The resulting surface receptor expression data were integrated into proteomic and transcriptomic NCI-60 datasets applying a sophisticated multiomics multiple co-inertia analysis (MCIA). This allowed us to identify surface profiles for skin, brain, colon, kidney, and bone marrow derived cell lines and cancer entity-specific cell surface receptor biomarkers for colon and renal cancer.
RESULTS: For colon cancer, identified biomarkers are CD15, CD104, CD324, CD326, CD49f, and for renal cancer, CD24, CD26, CD106 (VCAM1), EGFR, SSEA-3 (B3GALT5), SSEA-4 (TMCC1), TIM1 (HAVCR1), and TRA-1-60R (PODXL). Further data mining revealed that CD106 (VCAM1) in particular is a promising novel immunotherapeutic target for the treatment of renal cancer.
CONCLUSIONS: Altogether, our innovative multiomics analysis of the NCI-60 panel represents a highly valuable resource for uncovering surface receptors that could be further exploited for diagnostic and therapeutic purposes in the context of cancer immunotherapy.