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Identification of bacteria-derived HLA-bound peptides in melanoma
Shelly Kalaora1, Adi Nagler1, Deborah Nejman1
1Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Abstract:
A variety of species of bacteria are known to colonize human tumours1-11, proliferate within them and modulate immune function, which ultimately affects the survival of patients with cancer and their responses to treatment12-14. However, it is not known whether antigens derived from intracellular bacteria are presented by the human leukocyte antigen class I and II (HLA-I and HLA-II, respectively) molecules of tumour cells, or whether such antigens elicit a tumour-infiltrating T cell immune response. Here we used 16S rRNA gene sequencing and HLA peptidomics to identify a peptide repertoire derived from intracellular bacteria that was presented on HLA-I and HLA-II molecules in melanoma tumours. Our analysis of 17 melanoma metastases (derived from 9 patients) revealed 248 and 35 unique HLA-I and HLA-II peptides, respectively, that were derived from 41 species of bacteria. We identified recurrent bacterial peptides in tumours from different patients, as well as in different tumours from the same patient. Our study reveals that peptides derived from intracellular bacteria can be presented by tumour cells and elicit immune reactivity, and thus provides insight into a mechanism by which bacteria influence activation of the immune system and responses to therapy.
Insights
Intracellular bacteria in human tumors present peptides via human leukocyte antigen (HLA) molecules, potentially influencing cancer immunity and treatment responses. This study reveals bacterial antigens presented by tumor cells and eliciting immune reactions.
Area of Science:
- Oncology
- Immunology
- Microbiology
Background:
- Bacteria colonize human tumors, influencing patient survival and treatment outcomes.
- The presentation of bacterial antigens by tumor cells and their impact on anti-tumor immunity remain largely unknown.
Purpose of the Study:
- To investigate if intracellular bacterial antigens are presented by human leukocyte antigen class I and II (HLA-I and HLA-II) on melanoma cells.
- To determine if these bacterial antigens elicit a tumor-infiltrating T cell immune response.
Main Methods:
- 16S rRNA gene sequencing was employed to identify bacterial species within tumors.
- Human leukocyte antigen (HLA) peptidomics was used to analyze peptide repertoires presented on HLA-I and HLA-II molecules.
Main Results:
- Analysis of 17 melanoma metastases from 9 patients identified 248 unique HLA-I and 35 unique HLA-II peptides derived from 41 bacterial species.
- Recurrent bacterial peptides were found across different patients and within different tumors from the same patient.
- Evidence suggests that peptides from intracellular bacteria can be presented by tumor cells and trigger immune reactivity.
Conclusions:
- Intracellular bacteria-derived peptides are presented by melanoma cells via HLA-I and HLA-II molecules.
- This presentation can elicit an immune response, offering insights into how bacteria modulate the tumor immune microenvironment and affect therapy.
- Findings highlight a novel mechanism linking bacterial presence in tumors to immune activation and patient outcomes.

