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672 Identification of microbial-derived HLA-bound peptides in melanoma
  1. Adi Nagler1,
  2. Shelly Kalaora1,
  3. Deborah Gitta Rosenberg1,
  4. Michal Alon1,
  5. Eilon Barnea2,
  6. Ronen Levy1,
  7. Kevin Vervier3,
  8. Sophie Trabish1,
  9. Tali Dadosh1,
  10. Smadar Zaidman1,
  11. Leore Geller1,
  12. Polina Greenberg1,
  13. Neerupma Bhardwaj2,
  14. Alexandre Reuben4,
  15. Reetakshi Arora4,
  16. Michal Lotem5,
  17. Arie Admon2,
  18. Yishai Levin1,
  19. Trevor Lawley3,
  20. David Adams3,
  21. Naama Geva-Zatorsky2,
  22. Jennifer Wargo4,
  23. Ravid Straussman1 and
  24. Yardena Samuels1
  1. 1Weizmann Institute Of Science, rehovot, Israel
  2. 2Technion, Hifa, Israel
  3. 3Wellcome Sanger Institute, Cambridge, UK
  4. 4MD Anderson Cancer Center, Houston, TX, USA
  5. 5Hadassah Medical School, Jerusalem, Israel


Background The query for tumor shared and neo-antigens as a therapeutic approach has been the focus of cancer immunology for the past two decades. Notably, these peptide sequences can bind to HLA molecules and present on the cell surface, subsequently to be recognized by T-cell receptors (TCRs), activating the immune system and so facilitating in tumor rejection.1–3 The search for new origins of targetable types of HLA peptides is consistently growing, and new studies show peptides that are derived from non-canonical open reading frames (ORFs), altered translation, proteasome splicing, viral proteins and more.4–6 In light of the new findings, showing the important role of intra-tumor and gut bacteria in tumor-genesis and their effect on the immune response,7–10 we went on a quest for discovering whether intracellular bacteria antigens can be presented by tumor cells, and whether these antigens may elicit an immune response.

Methods Combination of HLA peptidomics with 16S rDNA sequencing.

Results Combination of HLA peptidomics with 16S rDNA sequencing of 17 melanoma metastasis derived from 9 different patients, lead us to the unbiased identification of an intracellular bacterial peptide repertoire presented on HLA-I and HLA-II molecules. We were able to validate these results by co-culturing the bacterial species identified by 16S sequencing with the patient derived melanoma cells, further validating the peptide’s presentation by preforming HLA peptidomics on the infected cells. Importantly, we were able to identify common bacterial peptides from different metastases of the same patient as well as from different patients. Some of the common bacterial peptides, as well as others, were able to elicit an immune response by the autologous tumor infiltrating lymphocytes (TILs), suggesting potential therapeutic implications of these peptides.

Conclusions The insights gathered through this study elucidate the effect of intra-tumor bacteria on the immune response and so, may lead to the development of novel clinical applications.


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