Proteomics

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Identification of microbial-derived HLA-bound peptides in melanoma


ABSTRACT: Various bacterial species are known to colonize human tumors , proliferate within them and modulate immune function, ultimately affecting patient survival and response to treatment. However, it is not known whether intracellular bacterial antigens are presented by HLA-I and HLA-II molecules of tumor cells, and whether potential tumor-presented bacterial-derived antigens may elicit a tumor infiltrating T-cell immune response. Here, we used 16S rRNA gene sequencing and HLA-peptidomics to unbiasedly identify an intracellular bacterial peptide repertoire presented on HLA-I and HLA-II molecules in melanoma tumors. Our microbial analysis of 17 melanoma metastases, derived from 9 patients, revealed 248 and 38 unique HLA-I and HLA-II peptides, respectively, derived from 41 different classified bacterial species. Recurrent bacterial peptides were identified in different tumors. Our study reveals that intra-tumor intracellular bacteria can be presented by tumor cells and elicit immune-reactivity, thus providing insight into how bacteria influence immune system activation and response to therapy.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): B Cell, Melanoma Cell, Cell Culture, Macrophage

DISEASE(S): Melanoma

SUBMITTER: Shelly Kalaora  

LAB HEAD: Prof. Yardena Samuels

PROVIDER: PXD022150 | Pride | 2021-02-04

REPOSITORIES: Pride

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Publications

Identification of bacteria-derived HLA-bound peptides in melanoma.

Kalaora Shelly S   Nagler Adi A   Nejman Deborah D   Alon Michal M   Barbolin Chaya C   Barnea Eilon E   Ketelaars Steven L C SLC   Cheng Kuoyuan K   Vervier Kevin K   Shental Noam N   Bussi Yuval Y   Rotkopf Ron R   Levy Ronen R   Benedek Gil G   Trabish Sophie S   Dadosh Tali T   Levin-Zaidman Smadar S   Geller Leore T LT   Wang Kun K   Greenberg Polina P   Yagel Gal G   Peri Aviyah A   Fuks Garold G   Bhardwaj Neerupma N   Reuben Alexandre A   Hermida Leandro L   Johnson Sarah B SB   Galloway-Peña Jessica R JR   Shropshire William C WC   Bernatchez Chantale C   Haymaker Cara C   Arora Reetakshi R   Roitman Lior L   Eilam Raya R   Weinberger Adina A   Lotan-Pompan Maya M   Lotem Michal M   Admon Arie A   Levin Yishai Y   Lawley Trevor D TD   Adams David J DJ   Levesque Mitchell P MP   Besser Michal J MJ   Schachter Jacob J   Golani Ofra O   Segal Eran E   Geva-Zatorsky Naama N   Ruppin Eytan E   Kvistborg Pia P   Peterson Scott N SN   Wargo Jennifer A JA   Straussman Ravid R   Samuels Yardena Y  

Nature 20210317 7852


A variety of species of bacteria are known to colonize human tumours<sup>1-11</sup>, proliferate within them and modulate immune function, which ultimately affects the survival of patients with cancer and their responses to treatment<sup>12-14</sup>. 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-infiltrati  ...[more]

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