Microbial peptides activate tumour-infiltrating lymphocytes in glioblastoma.
Microbial peptides activate tumour-infiltrating lymphocytes in glioblastoma.
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DOI：
10.1038/s41586-023-06081-w
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发表时间：
2023-05
期刊：
影响因子：
64.8
通讯作者：
Martin, Roland
中科院分区：
文献类型：
--
作者：
Naghavian, Reza;Faigle, Wolfgang;Oldrati, Pietro;Wang, Jian;Toussaint, Nora C.;Qiu, Yuhan;Medici, Gioele;Wacker, Marcel;Freudenmann, Lena K.;Bonte, 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
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. 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. Tumour-infiltrating lymphocytes from glioblastoma can recognize bacterial and gut microbial peptides.
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