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A variety of species of bacteria are known to colonize human tumours1,2,3,4,5,6,7,8,9,10,11, proliferate within them and modulate immune function, which ultimately affects the survival of patients with cancer and their responses to treatment12,13,14. 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.
Shelly Kalaora,Adi Nagler
Shelly Kalaora,Adi Nagler,Deborah Nejman,Michal Alon,Chaya Barbolin,Eilon Barnea,Steven L C Ketelaars,Kuoyuan Cheng,Kevin Vervier,Noam Shental,Yuval Bussi,Ron Rotkopf,Ronen Levy,Gil Benedek,Sophie Trabish,Tali Dadosh,Smadar Levin-Zaidman,Leore T Geller,Kun Wang,Polina Greenberg,Gal Yagel,Aviyah Peri,Garold Fuks,Neerupma Bhardwaj,Alexandre Reuben,Leandro Hermida,Sarah B Johnson,Jessica R Galloway-Peña,William C Shropshire,Chantale Bernatchez,Cara Haymaker,Reetakshi Arora,Lior Roitman,Raya Eilam,Adina Weinberger,Maya Lotan-Pompan,Michal Lotem,Arie Admon,Yishai Levin,Trevor D Lawley,David J Adams,Mitchell P Levesque,Michal J Besser,Jacob Schachter,Ofra Golani,Eran Segal,Naama Geva-Zatorsky,Eytan Ruppin,Pia Kvistborg,Scott N Peterson,Jennifer A Wargo,Ravid Straussman,Yardena Samuels