CD81 通过阻断 CD274/PD-L1 的选择性自噬降解驱动放射抵抗性胶质母细胞瘤的免疫逃逸
CD81 drives immune evasion in radioresistant glioblastoma by blocking selective autophagic degradation of CD274/PD-L1.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Microbial peptides activate tumour-infiltrating lymphocytes in glioblastoma.
Microbial peptides activate tumour-infiltrating lymphocytes in glioblastoma.
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微生物在人体众多生理过程中发挥关键作用,并且近期已被证明可改变对免疫检查点抑制剂的反应1,2。本文旨在探讨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角色。我们证明,胶质母细胞瘤组织和肿瘤细胞系的HLA分子均呈递细菌特异性肽。这一发现促使我们检验TIL(肿瘤浸润淋巴细胞)(TILs)是否识别肿瘤来源的细菌肽。从HLA II类分子洗脱的细菌肽可被TILs识别,尽管非常微弱。使用无偏倚抗原发现方法探究一个TIL CD4+ T细胞克隆的特异性,我们显示其识别来自致病菌、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。这些肽对批量TILs和外周血记忆细胞也具有强烈刺激作用,后者随后对肿瘤来源的靶肽产生反应。我们的数据提示细菌病原体和细菌肠道微生物群如何参与对肿瘤抗原的特异性免疫识别。对TILs微生物靶抗原的无偏倚鉴定为未来个性化肿瘤疫苗接种策略带来了希望。
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.
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