医学
伦瓦提尼
免疫检查点
头颈部鳞状细胞癌
转录组
彭布罗利珠单抗
靶向治疗
无容量
肿瘤科
头颈部癌
癌症研究
生物信息学
免疫疗法
计算生物学
癌症
内科学
生物
甲状腺癌
基因表达
基因
生物化学
作者
Andrew Causer,Xiao Tan,Xuehan Lu,Philip Moseley,Siok Min Teoh,Natalie Molotkov,Margaret McGrath,Tae Hyun Kim,Peter T. Simpson,Chris Perry,Ian H. Frazer,Benedict Panizza,Rahul Ladwa,Quan Nguyen,Jazmina L. Gonzalez-Cruz
标识
DOI:10.1038/s41698-023-00444-2
摘要
Abstract Immune checkpoint inhibitor (ICI) therapy has had limited success (<30%) in treating metastatic recurrent Head and Neck Oropharyngeal Squamous Cell Carcinomas (OPSCCs). We postulate that spatial determinants in the tumor play a critical role in cancer therapy outcomes. Here, we describe the case of a male patient diagnosed with p16 + OPSCC and extensive lung metastatic disease who failed Nivolumab and Pembrolizumab/Lenvatinib therapies. Using advanced integrative spatial proteogenomic analysis on the patient’s recurrent OPSCC tumors we demonstrate that: (i) unbiased tissue clustering based on spatial transcriptomics (ST) successfully detected tumor cells and enabled the investigation of phenotypic traits such as proliferation or drug-resistance genes in the tumor’s leading-edge and core; (ii) spatial proteomic imagining used in conjunction with ST ( SpiCi , Spatial Proteomics inferred Cell identification) can resolve the profiling of tumor infiltrating immune cells, (iii) ST data allows for the discovery and ranking of clinically relevant alternative medicines based on their interaction with their matching ligand-receptor. Importantly, when the spatial profiles of ICI pre- and post-failure OPSCC tumors were compared, they exhibited highly similar PD-1/PD-L1 low and VEGFA high expression, suggesting that these new tumors were not the product of ICI resistance but rather of Lenvatinib dose reduction due to complications. Our work establishes a path for incorporating spatial-omics in clinical settings to facilitate treatment personalization.
科研通智能强力驱动
Strongly Powered by AbleSci AI