小柯机器人

瑞士苏黎世大学Roland Martin研究组发现，微生物肽激活胶质母细胞瘤的肿瘤浸润淋巴细胞。2023年5月17日，《自然》杂志在线发表了这一最新研究成果。

研究人员旨在解决微生物的作用以及它们在针对胶质母细胞瘤的免疫反应性中的潜在作用。研究人员证明胶质母细胞瘤组织和肿瘤细胞系的HLA分子都存在细菌特异性肽。这一发现促使其研究肿瘤浸润淋巴细胞（TIL）是否能识别肿瘤衍生的细菌肽。从HLA II类分子中洗脱出来的细菌肽能被TIL识别，尽管非常弱。研究人员使用一种无偏倚的抗原发现方法来探测了一个TIL CD4⁺T细胞克隆的特异性，并表明它能识别来自致病性细菌、共生肠道微生物群和胶质母细胞瘤相关肿瘤抗原的广泛肽。这些肽对大量TIL和外周血记忆细胞也有强烈的刺激作用，然后它们对肿瘤衍生的目标肽作出反应。

这些数据暗示了细菌病原体和细菌性肠道微生物群如何参与肿瘤抗原的特定免疫识别。无偏倚地识别TIL的微生物目标抗原为未来个性化的肿瘤疫苗接种方法带来了希望。

据悉，微生物在人体的众多生理过程中具有关键作用，最近还被证明可以改变对免疫检查点抑制剂的反应。

附：英文原文

Title: Microbial peptides activate tumour-infiltrating lymphocytes in glioblastoma

Author: Naghavian, Reza, Faigle, Wolfgang, Oldrati, Pietro, Wang, Jian, Toussaint, Nora C., Qiu, Yuhan, Medici, Gioele, Wacker, Marcel, Freudenmann, Lena K., Bont, Pierre-Emmanuel, Weller, Michael, Regli, Luca, Amigorena, Sebastian, Rammensee, Hans-Georg, Walz, Juliane S., Brugger, Silvio D., Mohme, Malte, Zhao, Yingdong, Sospedra, Mireia, Neidert, Marian C., Martin, Roland

Issue&Volume: 2023-05-17

Abstract: Microbial organisms have key roles in numerous physiological processes in the human body and have recently been shown to modify the response to immune checkpoint inhibitors1,2. Here we aim to address the role of microbial organisms and their potential role in immune reactivity against glioblastoma. We demonstrate that HLA molecules of both glioblastoma tissues and tumour cell lines present bacteria-specific peptides. This finding prompted us to examine whether tumour-infiltrating lymphocytes (TILs) recognize tumour-derived bacterial peptides. Bacterial peptides eluted from HLA class II molecules are recognized by TILs, albeit very weakly. Using an unbiased antigen discovery approach to probe the specificity of a TIL CD4+ T cell clone, we show that it recognizes a broad spectrum of peptides from pathogenic bacteria, commensal gut microbiota and also glioblastoma-related tumour antigens. These peptides were also strongly stimulatory for bulk TILs and peripheral blood memory cells, which then respond to tumour-derived target peptides. Our data hint at how bacterial pathogens and bacterial gut microbiota can be involved in specific immune recognition of tumour antigens. The unbiased identification of microbial target antigens for TILs holds promise for future personalized tumour vaccination approaches.

DOI: 10.1038/s41586-023-06081-w

Source: https://www.nature.com/articles/s41586-023-06081-w

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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