Funded Project 01

01 | Funded Project

Identification of immunomodulatory mechanisms during glioblastoma treatment and progression – toward the development of novel treatment strategies

Funding Period: 01.01.2024 – 31.12.2025
Project Lead: Prof. Dr. Katrin Lamszus
University Hospital for Neurosurgery Hamburg

Project Description

Despite the groundbreaking success of immunotherapy in several types of cancer, in particular melanoma and lung cancer, clinical trials with immune checkpoint blockade (ICB) or other immunotherapy approaches have largely yielded disappointing results in glioblastoma (GBM) patients.

Nonetheless, there is ample evidence that an intrinsic T cell immune response exists in GBM, which can be markedly enhanced by immunotherapy, as proven by the response to neoadjuvant checkpoint blockade in a small subgroup of GBM patients. A major challenge to successful immunotherapy is the lack and insufficient presentation of tumor antigens, and the active immunosuppression exerted by GBM, which pertains to the local environment as well as the systemic periphery.

The goal of this project is to assess the dynamics of the tumor infiltrating lymphocytes and peripheral blood lymphocytes in primary and recurrent GBM and IDH mutant gliomas, and to track the clonal evolution of the T cell repertoire during standard chemo-radiotherapy as well as immunotherapy. In addition, we will analyze the tumor cells for mutations in antigen processing and presentation genes, and assess circulating cellular immune profiles as well as soluble immune biomarkers in GBM patient blood.

Collectively, these analyses will allow us to develop a better understanding of the complex and interconnected immune landscape in different groups of glioma patients. In addition, we aim to identify new therapeutic targets which could pave the way for the development of novel tailored immunotherapeutic strategies, relying on adoptive T cell transfer and/or blockade of immunosuppressive mechanisms.