Identification of bacteria-derived HLA-bound peptides in melanoma.
Identification of bacteria-derived HLA-bound peptides in melanoma.
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DOI：
10.1038/s41586-021-03368-8
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发表时间：
2021-04
期刊：
影响因子：
64.8
通讯作者：
中科院分区：
文献类型：
--
作者：
已知有多种细菌在人类肿瘤中定居、在其中繁殖并调节免疫功能，最终影响癌症患者的生存和他们对治疗的反应。然而，目前尚不清楚来自细胞内细菌的抗原是否是由肿瘤细胞的人类白细胞抗原I类和II类分子(分别为人类白细胞抗原I和II)递送的，或者这些抗原是否会引起肿瘤浸润性T细胞免疫反应。在这里，我们使用16S rRNA基因测序和人类白细胞抗原多肽组分来鉴定来自细胞内细菌的多肽库，该多肽库存在于黑色素瘤中的人类白细胞抗原-I和人类白细胞抗原-II分子上。我们对17例黑色素瘤转移瘤(来自9例患者)的分析揭示了来自41种细菌的248和35个独特的人类白细胞抗原-I和人类白细胞抗原-II多肽。我们在不同患者的肿瘤中以及同一患者的不同肿瘤中发现了复发的细菌肽。我们的研究揭示了来自细胞内细菌的多肽可以被肿瘤细胞提呈并引发免疫反应，从而为细菌影响免疫系统的激活和治疗反应的机制提供了洞察。
A variety of species of bacteria are known to colonize human tumours, proliferate within them and modulate immune function, which ultimately affects the survival of patients with cancer and their responses to treatment. 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.
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