Nature:肿瘤细菌多肽或为癌症免疫治疗提供新靶点
创作:mildbreeze 审核:mildbreeze 04月01日
  • 通过16S rRNA基因测序和HLA(人类白细胞抗原)多肽组学方法,分析9位患者的17个黑色素瘤转移瘤的瘤内菌群以及源于这些细菌的HLA呈递的多肽库;
  • 鉴定出41种瘤内细菌,并表明其能进入肿瘤细胞内;
  • 鉴定出源自瘤内细菌的248个HLA-I和35个HLA-II多肽,这类细菌多肽可被肿瘤细胞和肿瘤内的抗原呈递细胞所呈递,并能引发T细胞免疫反应;
  • 一些瘤内细菌和HLA呈递的细菌多肽,在同一患者的多个肿瘤以及在多个患者中反复出现。
主编推荐语
mildbreeze
肿瘤内定植的微生物可以影响肿瘤微环境,比如引发炎症反应或局部免疫抑制,从而影响机体的抗肿瘤免疫以及癌症治疗的效果。Nature最新发表来自以色列魏茨曼科学研究所团队的一项最新研究,发现源自瘤内细菌的抗原多肽可以被肿瘤细胞呈递给免疫系统,并能引起免疫反应,提示这类细菌多肽可能是一类新的肿瘤抗原,或能成为抗肿瘤免疫治疗的新靶点。
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Nature [IF:42.778]

Identification of bacteria-derived HLA-bound peptides in melanoma

黑色素瘤中的细菌衍生的HLA结合多肽的鉴定

10.1038/s41586-021-03368-8

03-17, Article

Abstract & Authors:展开

Abstract:收起
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.

First Authors:
Shelly Kalaora,Adi Nagler

Correspondence Authors:
Yardena Samuels

All Authors:
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

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