MicroEpitope: an atlas of immune epitopes derived from cancer microbiomes

Nucleic Acids Res. 2024 Oct 9:gkae877. doi: 10.1093/nar/gkae877. Online ahead of print.

Abstract

The majority of human cancers harbor molecular evidence of intratumoral microbiota. Microbiota-derived epitopes as molecular mimics of tumor antigens can bind human leukocyte antigen (HLA), thereby modulating host immunity. However, many questions remain regarding the mechanisms underlying the interactions between microbiota and the host's immune system in cancer. Here, MicroEpitope (http://bio-bigdata.hrbmu.edu.cn/MicroEpitope) was developed to provide and analyze the atlas of microbiota-derived epitopes in cancer. We manually collected available mass spectrometry (MS)-based HLA immunopeptidomes of 1190 samples across 24 cancer types. Alignment was performed against an in-house constructed theoretical library of human and intratumor microbiome encoded proteins, including 1298 bacterial and 124 viral species. Currently, MicroEpitope contains 51 497 bacteria and 767 virus-derived epitopes, mainly originating from Bacillus subtilis, Buchnera aphidicola and human cytomegalovirus. The common immunogenic features of epitopes were calculated, as well as their biochemical properties and the clinical relevance of corresponding bacteria and viruses across cancers. MicroEpitope also provides five analytical tools, and multiple visualization methods to facilitate understanding of the roles of microbiota-derived epitopes in cancer immunity. In summary, MicroEpitope represents a vital resource for investigating HLA-presented immunopeptidomes derived from cancer microbiomes, and could further enable rich insight in tumor antigen prioritization strategies.