Mechanistic insights into the interactions between cancer drivers and the tumour immune microenvironment

Genome Medicine

Research

Hrvoje Misetic¹  Francesca D. Ciccarelli¹  Mohamed Reda Keddar¹  Jean-Pierre Jeannon² 

[1] Cancer Systems Biology Laboratory, The Francis Crick Institute, NW1 1AT, London, UK;School of Cancer and Pharmaceutical Sciences, King’s College London, SE11UL, London, UK;Department of Head & Neck Surgery, Great Maze Pond, Guy’s Hospital, SE1 9RT, London, UK;

关键词: Cancer driver genes;    Cancer immunology;    Computational biology;    Head and neck cancer;    Functional networks;   

DOI  :  10.1186/s13073-023-01197-0

 received in 2023-01-14, accepted in 2023-05-25,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundThe crosstalk between cancer and the tumour immune microenvironment (TIME) has attracted significant interest in the latest years because of its impact on cancer evolution and response to treatment. Despite this, cancer-specific tumour-TIME interactions and their mechanistic insights are still poorly understood.MethodsHere, we compute the significant interactions occurring between cancer-specific genetic drivers and five anti- and pro-tumour TIME features in 32 cancer types using Lasso regularised ordinal regression. Focusing on head and neck squamous cancer (HNSC), we rebuild the functional networks linking specific TIME driver alterations to the TIME state they associate with.ResultsThe 477 TIME drivers that we identify are multifunctional genes whose alterations are selected early in cancer evolution and recur across and within cancer types. Tumour suppressors and oncogenes have an opposite effect on the TIME and the overall anti-tumour TIME driver burden is predictive of response to immunotherapy. TIME driver alterations predict the immune profiles of HNSC molecular subtypes, and perturbations in keratinization, apoptosis and interferon signalling underpin specific driver-TIME interactions.ConclusionsOverall, our study delivers a comprehensive resource of TIME drivers, gives mechanistic insights into their immune-regulatory role, and provides an additional framework for patient prioritisation to immunotherapy. The full list of TIME drivers and associated properties are available at http://www.network-cancer-genes.org.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

Fig. 1

41116_2023_37_Article_IEq291.gif

41116_2023_37_Article_IEq290.gif

41116_2023_37_Article_IEq289.gif

41116_2023_37_Article_IEq287.gif

41116_2023_37_Article_IEq286.gif

41116_2023_37_Article_IEq285.gif

41116_2023_37_Article_IEq283.gif

Fig. 1

41116_2023_37_Article_IEq279.gif

41116_2023_37_Article_IEq277.gif

41116_2023_37_Article_IEq275.gif

41116_2023_37_Article_IEq272.gif

41116_2023_37_Article_IEq271.gif

41116_2023_37_Article_IEq269.gif

41116_2023_37_Article_IEq252.gif

41116_2023_37_Article_IEq251.gif

41116_2023_37_Article_IEq250.gif

41116_2023_37_Article_IEq249.gif

41116_2023_37_Article_IEq248.gif

41116_2023_37_Article_IEq246.gif

41116_2023_37_Article_IEq245.gif

41116_2023_37_Article_IEq244.gif

41116_2023_37_Article_IEq233.gif

41116_2023_37_Article_IEq225.gif

41116_2023_37_Article_IEq215.gif

41116_2023_37_Article_IEq206.gif