西班牙巴塞罗那科技学院Nuria Lopez-Bigas和Abel Gonzalez-Perez共同合作，近期取得重要工作进展。他们研究提出了免疫治疗应答的五个潜在因素。相关研究成果2024年9月12日在线发表于《自然—遗传学》杂志上。

据介绍，只有一部分接受免疫检查点抑制剂（CPI）治疗的患者对治疗有反应，区分有反应者和无反应者是一项重大挑战。许多提出的CPI反应和存活的生物标志物可能代表了对肿瘤、其微环境或宿主相同方面的替代测量。因此，研究人员目前忽略了有多少真正独立的生物标志物。

通过对一组转移性肿瘤患者（n=479）的基因组学、转录组学和临床数据进行无偏分析，研究人员发现了五个正交的潜在因素：肿瘤突变负荷、T细胞有效浸润、微环境中转化生长因子-β活性、既往治疗和肿瘤增殖潜力。在所有肿瘤类型中观察到它们与CPI反应和生存率的关联，并在六个独立的队列中进行了验证（n=1491）。这五个潜在因素构成了一个参考框架，用于组织当前和未来关于CPI反应和生存生物标志物的知识。

附：英文原文

Title: Five latent factors underlie response to immunotherapy

Author: Usset, Joseph, Rosendahl Huber, Axel, Andrianova, Maria A., Batlle, Eduard, Carles, Joan, Cuppen, Edwin, Elez, Elena, Felip, Enriqueta, Gmez-Rey, Marina, Lo Giacco, Deborah, Martinez-Jimenez, Francisco, Muoz-Couselo, Eva, Siu, Lillian L., Tabernero, Josep, Vivancos, Ana, Muios, Ferran, Gonzalez-Perez, Abel, Lopez-Bigas, Nuria

Issue&Volume: 2024-09-12

Abstract: Only a subset of patients treated with immune checkpoint inhibitors (CPIs) respond to the treatment, and distinguishing responders from non-responders is a major challenge. Many proposed biomarkers of CPI response and survival probably represent alternative measurements of the same aspects of the tumor, its microenvironment or the host. Thus, we currently ignore how many truly independent biomarkers there are. With an unbiased analysis of genomics, transcriptomics and clinical data of a cohort of patients with metastatic tumors (n=479), we discovered five orthogonal latent factors: tumor mutation burden, Tcell effective infiltration, transforming growth factor-beta activity in the microenvironment, prior treatment and tumor proliferative potential. Their association with CPI response and survival was observed across all tumor types and validated across six independent cohorts (n=1,491). These five latent factors constitute a frame of reference to organize current and future knowledge on biomarkers of CPI response and survival.

DOI: 10.1038/s41588-024-01899-0

Source: https://www.nature.com/articles/s41588-024-01899-0