Immune system gene regulation perturbation has been found to be a major cause of the development of various types of cancer. Numbers of mechanisms contribute to gene expression regulation, thus, systematically identification of potential regulons of immune-related pathways is critical to cancer immunotherapy. Here, we comprehensively chart the landscape of transcription factors, microRNAs, RNA binding proteins and long noncoding RNAs regulation in 17 immune-related pathways across 33 cancers. The potential immunology regulons are likely to exhibit higher expressions in immune cells, show expression perturbations in cancer, and are significantly correlated with immune cell infiltrations. We also identify a panel of clinically relevant immunology regulons across cancers. Moreover, the regulon atlas of immune-related pathways helps prioritizing cancer-related genes (i.e. ETV7, miR-146a-5p, ZFP36 and HCP5). We further identified two molecular subtypes of glioma (cold and hot tumour phenotypes), which were characterized by differences in immune cell infiltrations, expression of checkpoints, and prognosis. Finally, we developed a user-friendly resource, ImmReg (http://bio-bigdata.hrbmu.edu.cn/ImmReg/), with multiple modules to visualize, browse, and download immunology regulation. Our study provides a comprehensive landscape of immunology regulons, which will shed light on future development of RNA-based cancer immunotherapies.
