Human brain tumors are complex ecosystems that are comprised of several cell types. From a general perspective, these cell types can be largely grouped between tumor and non-tumor cells, the stroma. Such distinction is at the core of Ismaïl Hermelo’s doctoral dissertation.
Tumors are currently recognized as a diverse community of cells that, collectively, generate an intercellular milieu known as the tumor microenvironment. To better understand brain tumor microenvironments, computational methods have permitted to isolate immune-related gene expression features from the whole tumor transcriptome.
Furthermore, experimental cellular membrane characterization methods like flow cytometry, central in his thesis, have uncovered hybrid immune cell phenotypes. For this finding, the combination of computational methods with experimental results proved to be key. The noncanonical myeloid are myeloid cells with lymphoid membrane receptors therefore exhibiting a hybrid, mosaic-like phenotype.
The relevance of data driven methods applied on experimental result analysis resides in performing deeper analyses on immune cell populations that are not fully known to date to brain tumor immunology field, thus within the brain tumor – immune – microenvironments. This is reflected on the limited success of novel immunotherapies showing remarkable efficacy in other solid tumors, while in primary malignant brain tumors, patient responses are not substantial.
Further deciphering of the cellular players in the tumor milieu will help to fundamentally understand which cells contribute to tumor progression, prevent anti-tumor cytotoxic clearance, or are in a defective activation state so that e.g. immune activating therapies can be developed.
“This study evinces how the brain tumor immune microenvironment mosaic can further be deciphered by leveraging computational methods for analysis”, Ismaïl Hermelo says.
Additionally, patient samples have conferred the opportunity to develop patient-derived tumor models ex vivo and in vitro. Patient-derived glioblastoma organoids, which better retain the stromal component of the original tumor, were used to test rapid diagnostic technologies. The other models established were the glioblastoma monolayer cell cultures. These cultures serve as advanced models enriched with the most malignant tumor cells and provide the opportunity to study tumor cell signaling and drug responsiveness. This highlights the importance of using appropriate patient-derived avatar models to enhance disease modeling in ex vivo or in vitro settings, particularly for downstream applications. Altogether, this work highlights the critical role of patient-derived material in advancing both fundamental and translational brain tumor research.
Ismaïl Hermelo conducted his doctoral research in the Computational Biology Group led by Professor Matti Nykter, in close collaboration with Cancer Immunology and Regulation Group, led by Docent Kirsi Rautajoki, and the Tampere University Hospital.
Public defence on Friday 11 July
The doctoral dissertation of MSc. Ismaïl Hermelo in the field of brain tumor immunology titled From Neoplastic Cells to Non-Canonical Immune Subsets in Human Brain Tumors will be publicly examined at the Faculty of Medicine and Health Technology at Tampere University at 16 o’clock on Friday 11.7.2025 at Kauppi campus, Arvo building, auditorium F114 (Arvo Ylpön katu 34). The Opponent will be Professor Alfredo Quiñones-Hinojosa from Mayo Clinic Florida. The Custos will be Professor Matti Nykter from Faculty of Medicine and Health Technology, Tampere University.