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This work highlights the complex interplay between tumor genetics and the immune microenvironment, and could completely rethink how we sequence or combine targeted therapies and immunotherapies in neuro-oncology! Kudos to all authors! 👏🔬 #NeuroOnc #Immunology #Glioblastoma

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While we often try to shut down MAPK/ERK signaling to stop cancer growth, in the context of GBM immunotherapy, tumor-intrinsic ERK activation is actually required to promote a powerful anti-tumor immune response. 💡🎓

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Tumor-intrinsic p-ERK acts like a beacon for the immune system. It ramps up interferon responses and promotes the infiltration of cancer-fighting T cells directly into the tumor. It also facilitates crucial interactions between GBM cells and microglia. ⚡🧬

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The screen identified the RAF-MEK-ERK axis as the STRONGEST modulator! Surprisingly, experimentally inducing ERK phosphorylation (p-ERK) in the tumor cells actually enhanced survival after anti-PD-1 and anti-CTLA-4 therapy, leading to durable immunity! 🛡️📈

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Anna Golebiewska @annagolebiewska.bsky.social · 12/06/2026

To figure out what make gliomas susceptible to ICB, we performed an in vivo kinome-wide CRISPR/Cas9 screen in murine models to find the genes that modulate tumor response to anti-PD-1 therapy and CD8+ T cell recognition. 🐁🔬

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Reposted by Yahaya Yabo

Preclinical modeling of the tumor microenvironment remains a challenge in #glioblastoma! Check out what is possible with #organoids in our new review in Seminars in Cancer Biology: doi.org/10.1016/j.se..., #LIH, #FnrLux , #TELEVIE, #NET4BRAIN,

doi.org

Redirecting

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Reposted by Yahaya Yabo

MILO Lab @milolab.bsky.social · 08/06/2026

Brain cancer is one of medicine’s most complex challenges. At the MILO Lab, we are working on decoding this complexity, from cellular interactions to computational patterns, to map the path to a breakthrough. 🧠✨

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Reposted by Yahaya Yabo

MILO Lab @milolab.bsky.social · 30/05/2026

A wonderful lab retreat bringing together scientific discussion, new ideas, collaboration, and plenty of laughter. Grateful for the opportunity to step away from the bench, reflect on our research, and strengthen the connections that make science possible! ✨🧬🔬

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Reposted by Yahaya Yabo

EANO @eanoassociation.bsky.social · 04/06/2026

👋 Students, Youngsters, Fellows, Postdocs, Nurses & AHP in #NeuroOncology! EANO invites you to register for the 21st Meeting of the European Association of Neuro-Oncology (#EANO2026) taking place from Sept 24-27, 2026 in Rome, IT. 👉 Register today! eano.eu/eano2026/reg... #btsm

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Reposted by Yahaya Yabo

Roel Verhaak @roelverhaak.bsky.social · 04/06/2026

In our new collaborative paper on IDHmutant glioma with the Tirosh, Suva, Iavarone and Lasorella labs, we show how acquired genetic alterations converge with cell state changes and poor treatment responses. www.nature.com/articles/s41...

nature.com

Acquired genetic and cell-state changes in IDH-mutant glioma progression - Nature

Longitudinal transcriptomic, chromatin and genomic analyses of the two types of IDH-mutant glioma reveal in detail how disease progression is influenced by interdependent genetic, epigenetic and micro...

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🧵 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.

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BACH2 dosage establishes the hierarchy of stemness and fine-tunes antitumor immunity in CAR T cells - Nature Immunology

🧵 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

doi.org

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.

🧵 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.

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🧵 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. 📉

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🧵 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?