Targeting immunosuppressive myeloid cells via implant-mediated slow release of small molecules to prevent glioblastoma recurrence

Article Article scientifique Article Targeting immunosuppressive myeloid cells via implant-mediated slow release of small molecules to prevent glioblastoma recurrence eng 2025-10-22 author Kaiser Yannik Center for Systems Biology, Massachusetts General Hospital, Boston, MA, USA. author Garris Christopher S 0000-0002-5764-6203 Center for Systems Biology, Massachusetts General Hospital, Boston, MA, USA.,Department of Pathology, Harvard Medical School, Boston, MA, USA. author Marinari Eliana Department of Oncology, University Hospital of Geneva, Geneva, Switzerland.,Center for Translational Research in Onco-Hematology, University of Geneva, Geneva, Switzerland.,Brain Tumor and Immune Cell Engineering Laboratory, AGORA Cancer Research Center, Lausanne, Switzerland.,Swiss Cancer Center Léman (SCCL), Geneva, Switzerland. 841772 Département de médecine (DEMED) author Kim Hyung Shik Center for Systems Biology, Massachusetts General Hospital, Boston, MA, USA. author Oh Juhyun Center for Systems Biology, Massachusetts General Hospital, Boston, MA, USA. author Pedard Martin Department of Oncology, University Hospital of Geneva, Geneva, Switzerland.,Center for Translational Research in Onco-Hematology, University of Geneva, Geneva, Switzerland.,Brain Tumor and Immune Cell Engineering Laboratory, AGORA Cancer Research Center, Lausanne, Switzerland.,Swiss Cancer Center Léman (SCCL), Geneva, Switzerland. 422242 Département de médecine (DEMED) author Halabi Elias A Center for Systems Biology, Massachusetts General Hospital, Boston, MA, USA. author Choi Moonhyun Center for Systems Biology, Massachusetts General Hospital, Boston, MA, USA. author Parvanian Sepideh Center for Systems Biology, Massachusetts General Hospital, Boston, MA, USA. author Kohler Rainer 0000-0001-6269-6590 Center for Systems Biology, Massachusetts General Hospital, Boston, MA, USA. author Migliorini Denis 0000-0003-0151-3222 Department of Oncology, University Hospital of Geneva, Geneva, Switzerland.,Center for Translational Research in Onco-Hematology, University of Geneva, Geneva, Switzerland.,Brain Tumor and Immune Cell Engineering Laboratory, AGORA Cancer Research Center, Lausanne, Switzerland.,Swiss Cancer Center Léman (SCCL), Geneva, Switzerland. 838158 Département de médecine (DEMED) author Weissleder Ralph 0000-0003-0828-4143 Center for Systems Biology, Massachusetts General Hospital, Boston, MA, USA. rweissleder@mgh.harvard.edu.,Department of Systems Biology, Harvard Medical School, Boston, MA, USA. rweissleder@mgh.harvard.edu. 10.1038/s41551-025-01533-2 41125869 2157-846X https://www.nature.com/articles/s41551-025-01533-2 Glioblastoma is a highly aggressive brain tumour with a high risk of recurrence after surgery, even when combined with chemotherapy and radiotherapy. A major barrier to lasting treatment is the tumour's immunosuppressive environment, which is largely dominated by myeloid cells. Here we describe the development of a biodegradable implant to sustainably release immune-modulator small molecules to reprogram tumour-infiltrating myeloid cells toward a pro-inflammatory, antitumour phenotype in the surgical cavity after tumour removal. In immunocompetent mouse models, this therapy induces interleukin-12 expression in myeloid cells without systemic cytokine elevation, and increases the infiltration of CD8<sup>+</sup> and CD4<sup>+</sup> T cells. Over 50% of mice treated (in combination with radiotherapy and chemotherapy) remain tumour-free during the experimental course (80 days). We further treated human glioblastoma explants ex vivo with the therapy and observed increased interleukin-12 expression in tumour-infiltrating myeloid cells, supporting the translational potential of this strategy. This implantable system offers a promising approach to prevent glioblastoma recurrence by activating innate immunity and sustaining immune surveillance post-surgery. Dewey 616 U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R33CA277820 U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R01CA281735 56 Département de médecine 221 false 1310 Tumeurs cérébrales 1016 Nature biomedical engineering 85459e51-e77f-473a-a30d-a8abd66e9171 Article (Published version) Public Article_scientifique_from_unpaywall.pdf 6237238 application/pdf CC BY-4.0 c3f5ee00516e12f9fcec032b40d21cad12bf16d2d285d8c3b80e6b580584f31e openAccess Faculté de médecine / Section de médecine clinique / Département de médecine

Title	Published in	Access level	OA Policy	Year	Views	Downloads

Targeting immunosuppressive myeloid cells via implant-mediated slow release of small molecules to prevent glioblastoma recurrence	Nature biomedical engineering			2025	31	17

Archive ouverte UNIGE

Pedard, Martin