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Immunostimulatory agonistic CD40 antibodies (\u03b1CD40) are in clinical development for solid tumors, but are yet to be evaluated for glioma. Here, we demonstrate that systemic delivery of \u03b1CD40 in preclinical glioma models induces the formation of tertiary lymphoid structures (TLS) in proximity of meningeal tissue. In treatment-na\u00efve glioma patients, the presence of TLS correlates with increased T cell infiltration. However, systemic delivery of \u03b1CD40 induces hypofunctional T cells and impairs the response to immune checkpoint inhibitors in pre-clinical glioma models. This is associated with a systemic induction of suppressive CD11b\n                    <jats:sup>+<\/jats:sup>\n                    B cells post-\u03b1CD40 treatment, which accumulate in the tumor microenvironment. Our work unveils the pleiotropic effects of \u03b1CD40 therapy in glioma and reveals that immunotherapies can modulate TLS formation in the brain, opening up for future opportunities to regulate the immune response.\n                  <\/jats:p>","DOI":"10.1038\/s41467-021-24347-7","type":"journal-article","created":{"date-parts":[[2021,7,5]],"date-time":"2021-07-05T06:04:04Z","timestamp":1625465044000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":163,"title":["Agonistic CD40 therapy induces tertiary lymphoid structures but impairs responses to checkpoint blockade in glioma"],"prefix":"10.1038","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0780-5827","authenticated-orcid":false,"given":"Luuk","family":"van Hooren","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Vaccaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohanraj","family":"Ramachandran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos","family":"Vazaios","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylwia","family":"Libard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiarne","family":"van de Walle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Georganaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilkka","family":"Pietil\u00e4","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8302-3253","authenticated-orcid":false,"given":"Joey","family":"Lau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria H.","family":"Ulvmar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5582-614X","authenticated-orcid":false,"given":"Mikael C. 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