Microbial organisms play a key role in numerous physiological processes in the human body and have been shown to modify the immune response. In fact, there is evidence on tumour shrinkage during bacterial infection and that immunotherapies are more effective when specific bacteria are present in the patients’ gut microbiome. This indicates that protective immune responses against bacteria may also target tumour tissue.

Reza Naghavian and his team addressed the role of microbial organisms and their potential involvement in immune reactivity against glioblastoma in the brain. The focus was on cancer-specific T cells as they are crucial for anti-tumour responses and successful immunotherapies. The researchers investigated T cell clones (TCCs), single T cell receptor, from tumour-infiltrating lymphocytes (TILs) in glioblastoma and investigated whether they recognize foreign antigens such as those from bacteria. They pursued several experimental paths to address if and how bacterial antigens contribute to immune reactivity against glioblastoma. For example, they established tumour-specific TCCs from TILs of a patient and examined their response to synthetically produced peptides derived from bacteria present in the tumour microenvironment.

The results are remarkable: The researchers showed that bacterial peptides in glioblastoma may be involved in tumoral immune responses through activation of certain TCCs. Through their broad antigen discovery approach, they subsequently defined a new set of peptides from pathogenic bacteria and gut microbiota that were strongly stimulatory for single TCCs and even bulk TILs. Finally, the data indicates that peripheral blood memory T cells stimulated and enriched with the newly identified bacterial antigens are capable of recognizing glioblastoma tumour cells.

The identification of bacteria, which have an active role in tumour defence mechanisms, and microbial peptides for T cell activation holds promise for strong anti-tumour responses. These important results pave the way for new personalized tumour vaccination approaches through synthetically produced bacterial peptides.

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, Roland MartinNature. Nature. 2023 May;617(7962):807-817