Identification of bacteria-derived HLA-bound peptides in melanoma

被引：290

作者：

Kalaora, Shelly ^{[1
]}

Nagler, Adi ^{[1
]}

Nejman, Deborah ^{[1
]}

Alon, Michal ^{[1
]}

Barbolin, Chaya ^{[1
]}

Barnea, Eilon ^{[2
]}

Ketelaars, Steven L. C. ^{[3
]}

Cheng, Kuoyuan ^{[4
]}

Vervier, Kevin ^{[5
]}

Shental, Noam ^{[6
]}

Bussi, Yuval ^{[1
,7
]}

Rotkopf, Ron ^{[8
]}

Levy, Ronen ^{[1
]}

Benedek, Gil ^{[9
]}

Trabish, Sophie ^{[1
]}

Dadosh, Tali ^{[10
]}

Levin-Zaidman, Smadar ^{[10
]}

Geller, Leore T. ^{[1
]}

Wang, Kun ^{[4
]}

Greenberg, Polina ^{[1
]}

Yagel, Gal ^{[1
]}

Peri, Aviyah ^{[1
]}

Fuks, Garold ^{[11
]}

Bhardwaj, Neerupma ^{[12
]}

Reuben, Alexandre ^{[13
]}

Hermida, Leandro ^{[4
]}

Johnson, Sarah B. ^{[13
,14
]}

Galloway-Pena, Jessica R. ^{[15
]}

Shropshire, William C. ^{[16
]}

Bernatchez, Chantale ^{[17
]}

Haymaker, Cara ^{[17
]}

Arora, Reetakshi ^{[13
,14
]}

Roitman, Lior ^{[1
]}

Eilam, Raya ^{[18
]}

Weinberger, Adina ^{[1
,7
]}

Lotan-Pompan, Maya ^{[1
,7
]}

Lotem, Michal ^{[19
]}

Admon, Arie ^{[2
]}

Levin, Yishai ^{[20
]}

Lawley, Trevor D. ^{[5
]}

Adams, David J. ^{[5
]}

Levesque, Mitchell P. ^{[21
]}

Besser, Michal J. ^{[22
,23
]}

Schachter, Jacob ^{[22
,24
]}

Golani, Ofra ^{[8
]}

Segal, Eran ^{[7
]}

Geva-Zatorsky, Naama ^{[12
,25
]}

Ruppin, Eytan ^{[4
]}

Kvistborg, Pia ^{[3
]}

Peterson, Scott N. ^{[26
]}

机构：

[1] Weizmann Inst Sci, Dept Mol Cell Biol, Rehovot, Israel

[2] Technion Israel Inst Technol, Dept Biol, Haifa, Israel

[3] Netherlands Canc Inst, Div Mol Oncol & Immunol, Amsterdam, Netherlands

[4] NCI, Canc Data Sci Lab CDSL, NIH, Bethesda, MD 20892 USA

[5] Wellcome Sanger Inst, Cambridge, England

[6] Open Univ Israel, Dept Math & Comp Sci, Raanana, Israel

[7] Weizmann Inst Sci, Dept Comp Sci & Appl Math, Rehovot, Israel

[8] Weizmann Inst Sci, Dept Life Sci Core Facil, Rehovot, Israel

[9] Hadassah Med Ctr, Tissue Typing & Immunogenet Unit, Jerusalem, Israel

[10] Weizmann Inst Sci, Dept Chem Res Support, Rehovot, Israel

[11] Weizmann Inst Sci, Dept Phys Complex Syst, Rehovot, Israel

[12] Technion Israel Inst Technol, Ruth & Bruce Rappaport Fac Med, Haifa, Israel

[13] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA

[14] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA

[15] Texas A&M Univ, Dept Vet Pathobiol, Houston, TX USA

[16] Univ Texas MD Anderson Canc Ctr, Dept Infect Dis, Houston, TX 77030 USA

[17] Univ Texas MD Anderson Canc Ctr, Dept Melanoma Med Oncol, Houston, TX 77030 USA

[18] Weizmann Inst Sci, Dept Vet Resources, Rehovot, Israel

[19] Hadassah Hebrew Univ, Sharett Inst Oncol, Med Ctr, Jerusalem, Israel

[20] Weizmann Inst Sci, Nancy & Stephen Grand Israel Natl Ctr Personalize, Botton Inst Prot Profiling, Rehovot, Israel

[21] Univ Zurich, Univ Zurich Hosp, Fac Med, Zurich, Switzerland

[22] Chaim Sheba Med Ctr, Ella Lemelbaum Inst Immuno Oncol & Melanoma, Tel Hashomer, Israel

[23] Tel Aviv Univ, Sackler Sch Med, Dept Clin Microbiol & Immunol, Tel Aviv, Israel

[24] Tel Aviv Univ, Sackler Sch Med, Tel Aviv, Israel

[25] Canadian Inst Adv Res CIFAR Azrieli Global Schola, MaRS Ctr, Toronto, ON, Canada

[26] Sanford Burnham Prebys Med Discovery Inst, La Jolla, CA USA

来源：

NATURE | 2021年 / 592卷 / 7852期

基金：

欧洲研究理事会; 以色列科学基金会;

关键词：

MHC CLASS-II; FUSOBACTERIUM-NUCLEATUM; TUMOR MICROBIOME; CTLA-4; BLOCKADE; CELLS; EXPRESSION; INDUCTION; APOPTOSIS; ANTIGENS; IMMUNITY;

D O I：

10.1038/s41586-021-03368-8

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

A variety of species of bacteria are known to colonize human tumours(1-11), proliferate within them and modulate immune function, which ultimately affects the survival of patients with cancer and their responses to treatment(12-14). 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.

引用

页码：138 / +

页数：25

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