The viral expression and immune status in human cancers and insights into novel biomarkers of immunotherapy

Background Viral infections are prevalent in human cancers and they have great diagnostic and theranostic values in clinical practice. Recently, their potential of shaping the tumor immune microenvironment (TIME) has been related to the immunotherapy of human cancers. However, the landscape of viral expressions and immune status in human cancers remains incompletely understood. Methods We developed a next-generation sequencing (NGS)-based pipeline to detect viral sequences from the whole transcriptome and used machine learning algorithms to classify different TIME subtypes. Results We revealed a pan-cancer landscape of viral expressions in human cancers where 9 types of viruses were detected in 744 tumors of 25 cancer types. Viral infections showed different tissue tendencies and expression levels. Multi-omics analyses further revealed their distinct impacts on genomic, transcriptomic and immune responses. Epstein-Barr virus (EBV)-infected stomach adenocarcinoma (STAD) and Human Papillomavirus (HPV)-infected head and neck squamous cell carcinoma (HNSC) showed decreased genomic variations, significantly altered gene expressions, and effectively triggered anti-viral immune responses. We identified three TIME subtypes, in which the Immune-Stimulation subtype might be the promising candidate for immunotherapy. EBV-infected STAD and HPV-infected HNSC showed a higher frequency of the Immune-Stimulation subtype. Finally, we constructed the eVIIS pipeline to simultaneously evaluate viral infection and immune status in external datasets. Conclusions Viral infections are prevalent in human cancers and have distinct influences on hosts. EBV and HPV infections combined with the TIME subtype could be promising biomarkers of immunotherapy in STAD and HNSC, respectively. The eVIIS pipeline could be a practical tool to facilitate clinical practice and relevant studies.

Automated summary

This study revealed the landscape of viral expressions in human cancers, their impact on genomic, transcriptomic, and immune responses, and the identification of three different immune microenvironment subtypes. Epstein-Barr virus (EBV) and Human Papillomavirus (HPV) infections, combined with specific immune subtypes, could serve as promising biomarkers for immunotherapy in stomach adenocarcinoma (STAD) and head and neck squamous cell carcinoma (HNSC). The developed eVIIS pipeline could be a practical tool for clinical practice and relevant studies.