A systematic pan-cancer analysis of intratumoral microbiota-derived epitopes to inform cancer immunotherapy and prevention
4 affiliations
- 1State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang Province 150081, China.
- 2State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Department of Pharmacology (StateKey Laboratory—Province Key Laboratories of Biomedicine—Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150081, China.
- 3School of Interdisciplinary Medicine and Engineering, Heilongjiang Academy of Medical Science, Harbin Medical University, Harbin 150081, China.
- 4Third Ward of Obstetrics and Gynecology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province 150086, China.
Abstract
Intratumoral microbial antigens, which mimic tumor antigens, can be presented by human leukocyte antigen (HLA) molecules, thereby eliciting antitumor immune responses. However, a comprehensive pan-cancer characterization of such molecularly mimicking microbial epitopes is still lacking. Here, we construct a pan-cancer microbial epitope landscape from 1190 samples across 24 cancer types. Pan-cancer analyses reveal that microbial epitopes exhibit higher hydrophobicity, aliphatic indices, and stability than human epitopes. Nine HLA-I alleles tend to bind microbial epitopes, and HLA-C alleles show a stronger tendency to present microbial epitopes than HLA-A and HLA-B alleles. Moreover, we reveal that microbial species capable of generating HLA-I epitopes are more prevalent in tumors, that broadly detected epitopes span more cancer types, and that multiple microbial genera generate numerous immunogenic epitopes. Notably, homologous microbial epitopes and tumor antigens elicit cross-reactive T cell responses, and experimental evidence demonstrates that microbial epitopes exhibit enhanced immunogenicity and antitumor efficacy. Overall, our findings provide a foundation for microbial epitope vaccine development, offering insights for cancer prevention and therapy.
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BibTeX
@article{li2026systematic,
title = {{A systematic pan-cancer analysis of intratumoral microbiota-derived epitopes to inform cancer immunotherapy and prevention}},
author = {Donghao Li and Hao Wang and Jiyu Guo and Feng Leng and Xinran Zhi and Manyu Gong and Mengqian Zeng and Kefan Liu and Yuhong Sun and Yongsheng Li and Ying Zhang and Juan Xu},
journal = {Science Advances},
year = {2026},
month = oct,
doi = {10.1126/sciadv.aee7661},
url = {https://www.science.org/doi/abs/10.1126/sciadv.aee7661},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - A systematic pan-cancer analysis of intratumoral microbiota-derived epitopes to inform cancer immunotherapy and prevention
AU - Donghao Li
AU - Hao Wang
AU - Jiyu Guo
AU - Feng Leng
AU - Xinran Zhi
AU - Manyu Gong
AU - Mengqian Zeng
AU - Kefan Liu
AU - Yuhong Sun
AU - Yongsheng Li
AU - Ying Zhang
AU - Juan Xu
PY - 2026
DA - 2026/10/28
JO - Science Advances
DO - 10.1126/sciadv.aee7661
UR - https://www.science.org/doi/abs/10.1126/sciadv.aee7661
AB - Intratumoral microbial antigens, which mimic tumor antigens, can be presented by human leukocyte antigen (HLA) molecules, thereby eliciting antitumor immune responses. However, a comprehensive pan-cancer characterization of such molecularly mimicking microbial epitopes is still lacking. Here, we construct a pan-cancer microbial epitope landscape from 1190 samples across 24 cancer types. Pan-cancer analyses reveal that microbial epitopes exhibit higher hydrophobicity, aliphatic indices, and stability than human epitopes. Nine HLA-I alleles tend to bind microbial epitopes, and HLA-C alleles show a stronger tendency to present microbial epitopes than HLA-A and HLA-B alleles. Moreover, we reveal that microbial species capable of generating HLA-I epitopes are more prevalent in tumors, that broadly detected epitopes span more cancer types, and that multiple microbial genera generate numerous immunogenic epitopes. Notably, homologous microbial epitopes and tumor antigens elicit cross-reactive T cell responses, and experimental evidence demonstrates that microbial epitopes exhibit enhanced immunogenicity and antitumor efficacy. Overall, our findings provide a foundation for microbial epitope vaccine development, offering insights for cancer prevention and therapy.
SN - 2375-2548
ER -