Tumor antigens and immune landscapes identification guided the development of colorectal cancer mRNA vaccines

Abstract

Abstract Colorectal cancer (CRC) is the third most common tumor and the second leading cause of cancer-related mortality. As an alternative to traditional cancer immunotherapy approaches, mRNA vaccines have gained significant attentio due to their numerous advantages. In this study, our objective was to screen for potential tumor antigens in CRC and identify mRNA vaccines capable of targeting specific immune subtypes based on their recognition of these immune subtypes. Through our research, We successfully identified eight overexpressed and mutated tumor antigens associated with poor prognosis in CRC, including ADAMTS4, LZTS1, OLR1, SLC11A1, SPOCD1, SPP1, STC1 and TIMP1. Then we assessed the association between these genes and the antigen-presenting immune cells. Furthermore, we identified three distinct immune subtypes of CRC, namely CRC immune subtype (CIS) 1–3. Among these subtypes, CIS3 exhibited a worse prognosis, a higher number of tumor mutations, and significantly lower immune activity compared to CIS1 and CIS2. Additionally, these above immune types were prominently linked to different immunocompetencies, immune genic cell death modulators and the prognostic factors in CRC. In summary, our findings conclusively identify three distinct immune subtypes of CRC and eight potential targets for CRC mRNA vaccines. These findings provide a new perspective on antigen selection and population stratification for future development and application of CRC mRNA vaccines.