Thanks Samir.

🧵 8/8 Together, these data map the rapid transcriptional and microenvironmental drivers of CAR-T dysfunction in glioblastoma and point to MAF and BACH2 as candidates for more durable CAR-T CELL effect.

BACH2 dosage establishes the hierarchy of stemness and fine-tunes antitumor immunity in CAR T cells - Nature Immunology One of three back-to-back papers to show that dosage of BACH2 can modulate T cell differentiation and function and how we might apply this to enhance CAR T cell therapies for cancer.

🧵 7/8 Our findings align with recent work in 3 back-to-back papers in Nature Immunology, highlighting BACH2's role in maintaining T cell fitness and its potential for enhancing CAR-T durability.
doi.org/10.1038/s41590-025-02388-0
doi.org/10.1038/s41590-025-02391-5
doi.org/10.1038/s41590-025-02389-z

🧵 6/8 Using gene regulatory network reconstruction and in silico perturbation, we identified MAF and BACH2 as key regulators of CD8 T cell state. MAF was enriched in CAR CD8 T cells with exhaustion-like features, while BACH2 was enriched in non-exhausted CD8 T cells indicating a protective role.

🧵 5/8 These myeloid cells were primarily tumor-associated macrophages with enhanced phagocytic and scavenger transcriptional programs. Spatially, they colocalized with mesenchymal-like glioblastoma cells within hypoxic tumor niches, suggesting a permissive niche for immunosuppression. 🗺️

🧵 4/8 Looking beyond the T cells, we found that interactions between myeloid cells and CAR CD8+ T cells shaped an immunosuppressive signaling environment. Pathways like TIGIT and SELPLG were upregulated, alongside altered CLEC-KLRB1 signaling, all linked to dysfunctional CD8 T cell states.

🧵 3/8 We profiled CAR-T cells using scRNA-seq to find out.
CAR CD8+ T cells adopted an effector-skewed activation state but also upregulated inhibitory receptors as well as an exhaustion-associated transcription factor program. Despite initial cytotoxicity, they showed early signs of dysfunction. 📉

🧵 2/8 We observed an early antitumor effect by treating glioblastoma cells with NKG2D-CAR-T cells in our model. But this response was short-lived, mirroring the limited therapeutic durability seen in glioblastoma patients following CAR-T treatment.

The question is, what is driving this failure?

🧵 1/8 Hot off the press! 🔥 link.springer.com/article/10.1...

CAR-T cells show promising results in preclinical glioblastoma models, yet clinical benefit in patients has been limited. To understand why, we used a human brain slice model that preserves the native human GBM tumor microenvironment. 🧠

Modelling brain tumours with organoids: towards precision medicine in neuro-oncology - Nature Reviews Neurology Organoids provide a useful model to capture the heterogeneity of brain tumours. Here, the authors assess current methodologies for generating organoids from various types of brain tumour and discuss h...

How can brain tumor organoids advance research, drug efficacy studies, and precision medicine? Check out our new review in Nature Reviews Neurology. doi.org/10.1038/s415...
@LIH_Luxembourg , @glioresolve.bsky.social, @FnrLux, #NET4BRAIN

Happy to see this amazing work finally out. We used our NePSTA model to acurately predict the epigenetic subtypes of meningiomas based on cell-type abundance in subgraphs containing gene expression features + spatial adjacency.

Immunosuppressive mechanisms and therapeutic interventions shaping glioblastoma immunity - Nature Cancer In this Review, Golebiewska and colleagues summarize the main features of the immunosuppressive microenvironment in glioblastoma (GBM) and discuss how different therapeutic approaches reshape GBM immu...

Can immunotherapy ever work in #glioblastoma?

In a new #NatureCancer review, we share our perspective on current limitations and future directions:
www.nature.com/articles/s43...

#NORLUX, #LIH , @fnr.lu #TELEVIE, @glioresolve.bsky.social, @michael-platten.bsky.social

Serotonergic neuron-glioma interactions drive high-grade glioma pathophysiology High-grade gliomas are lethal brain cancers that are powerfully regulated by glutamatergic neurons through activity-dependent paracrine factors and functional neuron-to-glioma synapses. Here, we repor...

www.biorxiv.org/content/10.6...

Happy to share a new #NORLUX study on how humanized patient-derived xenografts of #glioblastoma can be useful in investigating immunosuppression and clinically-relevant immunotherapy testing. See for more: www.biorxiv.org/content/10.1...
#immunotherapy, #preclinicalmodeling,

Amazing Keynote talk by @heilandhenrik.bsky.social on "Translational Data Integration and Technological Developments in Neuro-Oncology" at the ongoing #SNO2025 in Hawaii.🧠

Be sure to check the @milolab.bsky.social talks including our work on "Deciphering spatiotemporal trajectories of tissue adaptation after surgical resection of glioblastoma."

#EANO2025 was awesome. Great time interacting with mentors and colleagues. Looking forward to another exciting meeting.

Just wrapped up an incredible few days in Prague for the @eanoassociation.bsky.social meeting! Truly inspiring sessions, great discussions, and exciting new collaborations. The MILO Lab shined with engaging talks and eye-catching posters! Ready to keep pushing the boundaries of science together!

📢 @eanoassociation.bsky.social 2025 kicks off today in Prague!

Proud to see strong #EORTC representation with six abstracts and a joint session with BTG featuring EORTC-led projects on clinical trial planning.

More info 👉 www.eortc.org/blog/2025/10...

#EANO2025 #NeuroOncology @qol.eortc.org

Integrative multi-omics combined with functional pharmacological profiling in patient-derived organoids identifies personalized therapeutic vulnerabilities of adult high-grade gliomas Background: Precision medicine has transformed cancer treatment by tailoring therapies to specific molecular aberrations. Integrating high-resolution multi-omics with high-throughput functional profil...

Precision medicine in high-grade gliomas? Using high-throughput drug screen in #NORLUX patient-derived organoids multi-omics and machine learning, we assessed pharmacogenomics: www.biorxiv.org/content/10.1...
@fnr.lu, #precisionmedicine, #organoids, #drugscreen, #pharmacogenomics, #braintumors

Thanks Roman.

NEW content online!

Happy to share a short "tools of the trade" piece on our NeuroPathology Spatial Transcriptomic Analysis (NePSTA) tool. Now available @natrevcancer.nature.com www.nature.com/articles/s41...

#microglia and other tissue #macrophages are highly plastic. This makes them look differently depending on their respective context. Granular methods like #single-cell sequencing are merely snapshots that may simplify the complexity found in the tissue. In our perspective in @natneuro.nature.com

How does tumour heterogeneity arise? How can we predict cancer cell plasticity? In 2 new studies, we trace #glioblastoma heterogeneity to a spatial cancer cell trajectory w. multimodal cell atlassing bit.ly/4mkrWgs & predict plasticity w. snRNA/ATAC+deep learning bit.ly/3FbI6Ic 🧵

Decoding Plasticity Regulators and Transition Trajectories in Glioblastoma with Single-cell Multiomics Glioblastoma (GB) is one of the most lethal human cancers, marked by profound intratumoral heterogeneity and near-universal treatment resistance. Cellular plasticity, the capacity of cancer cells to t...

Two massive glioblastoma papers, datasets, trajectories, insights, and.. a very cool new method for GRN inference - scDORI -from @steglelab.bsky.social @oliverstegle.bsky.social @bayraktarlab.bsky.social & Moritz Mall www.biorxiv.org/content/10.1... www.biorxiv.org/content/10.1...

The multilayered transcriptional architecture of glioblastoma ecosystems - Nature Genetics Integrated single-cell transcriptomic and genetic characterization of 121 adult glioblastomas identifies heterogeneity at cell type, cell state and baseline expression program levels associated with s...

1/ Thrilled to share our TWO back-to-back papers published in Nature Genetics today! www.nature.com/articles/s41... , www.nature.com/articles/s41...

Finally, the GBmap paper is out after over 80 citations of the preprint version. Congratulations @ccruizm.bsky.social 🎉

Putting cancer immunotherapy into spatial context in the clinic - Nature Biotechnology Spatial omics technologies offer insights into the organization of cellular and molecular components and their interactions within the tumor ecosystem. Overcoming the key challenges to integrating the...

Putting cancer immunotherapy into spatial context in the clinic - @joakimlundeberg.bsky.social @scilifelab.se @ki.se go.nature.com/4jlus4b

The @milolab.bsky.social retreat was lit 🔥. I am grateful and lucky to be in this amazing group.
Great people, great science.
#glioblastoma #spatialtranscriptomics
#scRNA-seq