Microbial peptides activate tumour-infiltrating lymphocytes in glioblastoma

Reza Naghavian, Wolfgang Faigle, Pietro Oldrati, Jian Wang, Nora C. Toussaint, Yuhan Qiu, Gioele Medici, Marcel Wacker, Lena K. Freudenmann, Pierre-Emmanuel Bonté, Michael Weller, Luca Regli, Sebastian Amigorena, Hans-Georg Rammensee, Juliane S. Walz, Silvio D. Brugger, Malte Mohme, Yingdong Zhao, Mireia Sospedra, Marian C. Neidert and Roland Martin ()
Additional contact information
Reza Naghavian: University of Zurich, University Hospital Zurich
Wolfgang Faigle: University of Zurich, University Hospital Zurich
Pietro Oldrati: University of Zurich, University Hospital Zurich
Jian Wang: University of Zurich, University Hospital Zurich
Nora C. Toussaint: ETH Zurich
Yuhan Qiu: University of Zurich, University Hospital Zurich
Gioele Medici: University Hospital Zurich, University of Zurich
Marcel Wacker: University of Tübingen, University Hospital Tübingen
Lena K. Freudenmann: University of Tübingen
Pierre-Emmanuel Bonté: PSL University, INSERM U932
Michael Weller: University Hospital Zurich, University of Zurich
Luca Regli: University Hospital Zurich, University of Zurich
Sebastian Amigorena: PSL University, INSERM U932
Hans-Georg Rammensee: University of Tübingen
Juliane S. Walz: University of Tübingen, University Hospital Tübingen
Silvio D. Brugger: University Hospital Zurich, University of Zurich
Malte Mohme: University Hospital Hamburg Eppendorf, University of Hamburg
Yingdong Zhao: Computational and Systems Biology Branch, Biometric Research Program, Division of Cancer Treatment and Diagnosis, NCI, NIH
Mireia Sospedra: University of Zurich, University Hospital Zurich
Marian C. Neidert: University Hospital Zurich, University of Zurich
Roland Martin: University of Zurich, University Hospital Zurich

Nature, 2023, vol. 617, issue 7962, 807-817

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41586-023-06081-w

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