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 inhibitors^1,2. 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.

微生物在人体的众多生理过程中发挥着关键作用，最近已被证明可以改变对免疫检查点抑制剂的反应^1,2 。在这里，我们的目标是解决微生物的作用及其在针对胶质母细胞瘤的免疫反应中的潜在作用。我们证明胶质母细胞瘤组织和肿瘤细胞系的 HLA 分子均呈现细菌特异性肽。这一发现促使我们检查肿瘤浸润淋巴细胞（TIL）是否识别肿瘤来源的细菌肽。 TIL 可识别从 HLA II 类分子洗脱的细菌肽，尽管识别能力非常弱。使用无偏见的抗原发现方法来探测 TIL CD4 ⁺ T 细胞克隆的特异性，我们发现它可以识别来自病原菌、共生肠道微生物群以及胶质母细胞瘤相关肿瘤抗原的广谱肽。这些肽还强烈刺激大量 TIL 和外周血记忆细胞，然后这些细胞会对肿瘤衍生的靶肽做出反应。我们的数据暗示细菌病原体和细菌肠道微生物群如何参与肿瘤抗原的特异性免疫识别。 TIL 微生物靶抗原的公正鉴定为未来个性化肿瘤疫苗接种方法带来了希望。