小柯机器人

以色列魏兹曼科学研究所Yardena Samuels研究组取得最新进展。他们对黑色素瘤中细菌来源的人白细胞抗原（HLA）结合肽进行了鉴定。相关论文发表在2021年2月17日出版的《自然》杂志上。

他们使用16S rRNA基因测序和HLA肽组学来鉴定源自细胞内细菌的肽库，该肽库已出现在黑素瘤肿瘤中的HLA-I和HLA-II分子上。他们对17个黑色素瘤转移瘤（来自9例患者）的分析表明，分别来自248种细菌的248和35种独特的HLA-I和HLA-II肽。他们在不同患者的肿瘤以及同一患者的不同肿瘤中鉴定出了复发性细菌肽。

他们的研究表明，肿瘤细胞可呈递源自细胞内细菌肽，并引发免疫反应，从而有助深入了解细菌影响免疫系统激活和对治疗反应的机制。

据了解，已知多种细菌会定植于人类肿瘤，在其中扩散并调节免疫功能，最终影响癌症患者的生存及其对治疗的反应。然而，尚不清楚源自细胞内细菌的抗原是否由肿瘤细胞的HLA-1和HLA-II分子呈递，或此类抗原是否引起肿瘤浸润性T细胞免疫反应。

附：英文原文

Title: Identification of bacteria-derived HLA-bound peptides in melanoma

Author: 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-Pea, 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

Issue&Volume: 2021-03-17

Abstract: 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.

DOI: 10.1038/s41586-021-03368-8

Source: https://www.nature.com/articles/s41586-021-03368-8

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