Lausanne Researchers Combine 10x Genomics' Chromium and Xenium for Novel Insights into Resistance and Potential Therapeutics for Brain Cancer
Researchers from the University of Lausanne and Ludwig Institute for Cancer Research used 10x Genomics' Chromium and Xenium platforms to study glioblastoma (GBM) recurrence mechanisms. The study, published in Cancer Cell, revealed that fibrotic scars in the brain contain dormant tumor cells, potentially seeding GBM recurrence. By combining single-cell and spatial transcriptomics, researchers identified pericyte-derived fibroblast-like cells as key players in scar formation.
The team developed a three-drug treatment regimen targeting CSF-1R and inhibiting scar formation, which significantly improved survival in preclinical mouse trials. Only 1 in 18 mice experienced tumor recurrence, marking a substantial improvement over conventional treatments. This research highlights the potential of combining 10x Genomics' technologies to develop novel therapeutic approaches for aggressive cancers like GBM.
I ricercatori dell'Università di Losanna e del Ludwig Institute for Cancer Research hanno utilizzato le piattaforme Chromium e Xenium di 10x Genomics per studiare i meccanismi di ricorrenza del glioblastoma (GBM). Lo studio, pubblicato su Cancer Cell, ha rivelato che le cicatrici fibrotiche nel cervello contengono cellule tumorali dormienti, che potrebbero innescare la ricorrenza del GBM. Combinando la trascrittomica monocellulare e spaziale, i ricercatori hanno identificato delle cellule simili a fibroblasti derivate dai periciti come attori chiave nella formazione delle cicatrici.
Il team ha sviluppato un regime di trattamento con tre farmaci mirato al CSF-1R per inibire la formazione di cicatrici, che ha significativamente migliorato la sopravvivenza nei trial preclinici su topi. Solo 1 su 18 topi ha mostrato recidiva tumorale, segnando un miglioramento sostanziale rispetto ai trattamenti convenzionali. Questa ricerca evidenzia il potenziale di combinare le tecnologie di 10x Genomics per sviluppare nuove strategie terapeutiche per tumori aggressivi come il GBM.
Investigadores de la Universidad de Lausana y del Instituto Ludwig de Investigación del Cáncer utilizaron las plataformas Chromium y Xenium de 10x Genomics para estudiar los mecanismos de recurrencia del glioblastoma (GBM). El estudio, publicado en Cancer Cell, reveló que las cicatrices fibróticas en el cerebro contienen células tumorales inactivas, que podrían propiciar la recurrencia del GBM. Al combinar la transcriptómica de una sola célula y espacial, los investigadores identificaron células derivadas de fibroblastos similares a pericitos como jugadores clave en la formación de cicatrices.
El equipo desarrolló un régimen de tratamiento de tres fármacos dirigido al CSF-1R e inhibiendo la formación de cicatrices, lo que mejoró significativamente la supervivencia en ensayos preclínicos en ratones. Solo 1 de 18 ratones experimentó recurrencia tumoral, marcando una mejora sustancial en comparación con tratamientos convencionales. Esta investigación destaca el potencial de combinar las tecnologías de 10x Genomics para desarrollar enfoques terapéuticos novedosos para cánceres agresivos como el GBM.
로잔 대학교와 루드비히 암 연구소의 연구자들은 10x Genomics의 Chromium 및 Xenium 플랫폼을 사용하여 교모세포종(GBM)의 재발 메커니즘을 연구했습니다. Cancer Cell에 발표된 이 연구는 뇌의 섬유성 흉터에 잠복해 있는 암세포가 GBM 재발을 유발할 수 있음을 밝혀냈습니다. 단일 세포 및 공간 전사체학을 결합하여 연구자들은 흉터 형성의 핵심 역할을 하는 주변세포 유래 섬유아세포 유사 세포를 확인했습니다.
팀은 CSF-1R을 표적으로 하고 흉터 형성을 억제하는 3약물 치료 요법을 개발하여 비임상 쥐 실험에서 생존을 크게 개선했습니다. 18마리 중 단 1마리만이 종양 재발을 경험했으며, 이는 기존 치료 방법에 비해 상당한 개선을 나타냅니다. 이 연구는 10x Genomics의 기술을 결합하여 GBM과 같은 공격적인 암에 대한 새로운 치료 접근법을 개발할 수 있는 잠재력을 강조합니다.
Des chercheurs de l'Université de Lausanne et de l'Institut Ludwig de recherche sur le cancer ont utilisé les plateformes Chromium et Xenium de 10x Genomics pour étudier les mécanismes de récidive du glioblastome (GBM). L'étude, publiée dans Cancer Cell, a révélé que les cicatrices fibreuses dans le cerveau contiennent des cellules tumorales dormantes, susceptibles de favoriser la récidive du GBM. En combinant la transcriptomique unicellulaire et spatiale, les chercheurs ont identifié des cellules semblables à des fibroblastes dérivées des péricytes comme acteurs clés dans la formation des cicatrices.
L'équipe a développé un régime de traitement à trois médicaments ciblant le CSF-1R et inhibant la formation de cicatrices, ce qui a considérablement amélioré la survie lors d'essais précliniques sur des souris. Seule 1 souris sur 18 a connu une récidive tumorale, marquant une amélioration substantielle par rapport aux traitements conventionnels. Cette recherche met en évidence le potentiel de combiner les technologies de 10x Genomics pour développer de nouvelles approches thérapeutiques contre des cancers agressifs comme le GBM.
Forscher der Universität Lausanne und des Ludwig-Instituts für Krebsforschung nutzten die Chromium- und Xenium-Plattformen von 10x Genomics, um die Mechanismen der Rezidivbildung bei Glioblastomen (GBM) zu untersuchen. Die in Cancer Cell veröffentlichte Studie zeigte, dass fibrotische Narben im Gehirn schlafende Tumorzellen enthalten, die möglicherweise die GBM-Rezidive begünstigen. Durch die Kombination von Einzelzell- und räumlicher Transkriptomik identifizierten die Forscher perizytenabgeleitete fibroblast-ähnliche Zellen als Schlüsselspieler bei der Narbenbildung.
Das Team entwickelte ein Dreifachmedikationsregime, das auf CSF-1R abzielt und die Narbenbildung hemmt, was die Überlebensrate in präklinischen Mausversuchen signifikant verbesserte. Nur 1 von 18 Mäusen erlebte eine Tumorrezidiv, was eine erhebliche Verbesserung gegenüber herkömmlichen Behandlungen darstellt. Diese Forschung hebt das Potenzial hervor, die Technologien von 10x Genomics zu kombinieren, um neuartige therapeutische Ansätze für aggressive Krebserkrankungen wie GBM zu entwickeln.
- 10x Genomics' Chromium and Xenium platforms were featured in a Cancer Cell cover article, enhancing the company's scientific reputation
- The study using 10x Genomics' technologies led to the development of a promising three-drug treatment regimen for glioblastoma in preclinical trials
- The research demonstrated the synergistic value of integrating 10x Genomics' single-cell and spatial technologies for cancer research
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Insights
This study marks a significant breakthrough in understanding glioblastoma (GBM) recurrence and potential treatment strategies. The researchers' novel approach of combining single-cell and spatial technologies has unveiled important insights into the role of fibrotic scars in GBM recurrence. The discovery that these scars contain dormant tumor cells and exhausted T cells provides a new perspective on why current treatments often fail.
The identification of pericyte-derived fibroblast-like cells as key players in scar formation opens up new avenues for targeted therapies. The three-drug regimen developed by the team, combining a CSF-1R inhibitor with two scar formation inhibitors, shows remarkable promise. With only
This research represents a significant opportunity for 10x Genomics (Nasdaq: TXG). The study's reliance on their Chromium and Xenium platforms showcases the company's technological prowess and the unique insights their tools can provide. This high-profile publication in Cancer Cell serves as a powerful marketing tool, potentially driving increased adoption of 10x Genomics' technologies in cancer research.
Moreover, the promising results of the preclinical trials could lead to increased investment in GBM research using 10x Genomics' platforms. If this approach translates to human trials, it could significantly expand the market for their technologies in both research and clinical settings. Investors should monitor for any announcements of partnerships or increased sales in the oncology research sector as a result of this breakthrough.
This research represents a paradigm shift in our understanding of GBM recurrence and treatment. The discovery of fibrotic scars as potential reservoirs for tumor recurrence challenges our current treatment approaches. The study's findings suggest that we need to rethink our strategies for post-treatment care in GBM patients.
The three-drug regimen's success in preclinical trials is particularly exciting. By targeting both CSF-1R and scar formation, this approach addresses multiple aspects of GBM biology simultaneously. However, it's important to temper enthusiasm with caution. While the results in mice are promising, human trials will be necessary to confirm efficacy and safety. If successful, this could be a game-changer for GBM treatment, potentially improving the dismal
In the September 9 cover article of Cancer Cell, researchers integrated 10x single cell and spatial technologies to identify a mechanism of glioblastoma recurrence in mice and develop a promising potential therapeutic approach.
GBM is both the most common brain cancer and the most aggressive, with a five-year survival rate of less than
Using a mouse model of GBM as their starting point, the team first noticed that all GBM treatments they tested were associated with fibrosis – a type of scarring – in the brain. Notably, all recurrent tumors were found immediately adjacent to these fibrotic scars; high-plex protein analysis indicated these scars contained dormant tumor cells that the researchers believe act as seeds for GBM recurrence. They next used Chromium Single Cell Gene Expression to characterize cell populations in fibrotic scars at several time points post-treatment, then turned to single cell spatial transcriptomics with Xenium In Situ to reveal the location of cells within the scars.
"Assessing how the glioblastoma microenvironment responded to treatment was extremely challenging, because the spatial localization of all the cell types was so important," said Dr. Spencer Watson, co-first author and postdoctoral fellow in the Joyce lab at the University of Lausanne. "We generated very rich datasets: mass-spec proteomics, HIFI digital pathology and Chromium single cell RNA-seq. But what made all these disparate data so powerful was integrating them all together with Xenium single cell spatial transcriptomics. This allowed us to analyze the biology holistically, in ways that no single technique could do on its own."
Normally, T cells act to kill cancer cells. However, the data they generated using Xenium showed that while T cells interacted with GBM tumor cells throughout the tissue, the T cells inside fibrotic scars were much more likely to be exhausted (e.g. non-functional). This raised the possibility that these scars not only contained residual tumor cells but helped protect them from immune recognition, acting like a reservoir for GBM recurrence and presenting a potential therapeutic target.
Combining Xenium and Chromium, the researchers found that genes associated with the formation of these scars were highest in one specific cell type: pericyte-derived fibroblast-like cells. Focusing on these cells, they identified two critical pathways linked to scar formation that spiked seven days post-treatment, but dropped back down after fourteen days, suggesting therapeutic relevance for inhibiting fibrotic scar formation.
Using Chromium to narrow down potential druggable targets, the Joyce lab created a three-drug treatment regimen consisting of a CSF-1R inhibitor and two different drugs inhibiting scar formation. Over long-term preclinical trials, these drugs had little effect when administered separately. When combined, however, these treatments led to a dramatic increase in survival in mice, with only 1 in 18 mice experiencing tumor recurrence over the several-month-long trial – a vast improvement compared to conventional treatments. Professor Joyce said, "Strategies such as these to limit fibrotic scarring could significantly improve outcomes for GBM patients receiving surgical, radiation, or macrophage-targeting therapies; this is an area of active investigation in my lab."
Ben Hindson, Co-Founder and Chief Scientific Officer of 10x Genomics, said, "This paper by Watson, Zomer, Joyce, and colleagues is a powerful example of how integrating Xenium single cell spatial and Chromium scRNA-seq can completely reshape our understanding of cancer dynamics. Seeing not just how cancer develops, but where and in what context, enabled these researchers to develop a potential therapy in their preclinical work by leveraging the strengths and synergies of different technologies to generate insights that simply aren't possible with a single platform. Advances like these are why we continuously drive innovation to help researchers move science forward."
To learn more about the study, read the full article.
About 10x Genomics
10x Genomics is a life science technology company building products to accelerate the mastery of biology and advance human health. Our integrated solutions include instruments, consumables and software for single cell and spatial biology, which help academic and translational researchers and biopharmaceutical companies understand biological systems at a resolution and scale that matches the complexity of biology. Our products are behind breakthroughs in oncology, immunology, neuroscience and more, fueling powerful discoveries that are transforming the world's understanding of health and disease. To learn more, visit 10xgenomics.com or connect with us on LinkedIn or X (Twitter).
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