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.
PLEASANTON, Calif., Sept. 10,
2024 /PRNewswire/ -- 10x Genomics, Inc.
(Nasdaq: TXG), a leader in single cell and spatial biology,
announced today that its Chromium Single Cell Gene Expression and
Xenium In Situ platforms were used in a publication – featured on
the cover of Cancer Cell – that sheds light on the role of
fibrotic scars in glioblastoma treatment recurrence. The study, led
by researchers in the laboratory of Professor Johanna Joyce (University of Lausanne,
Switzerland) and the Ludwig
Institute for Cancer Research (Lausanne, Switzerland), also showcased how inhibiting
both colony stimulating factor 1 receptor (CSF-1R; a therapeutic
target under investigation for treating multiple cancers, including
glioblastoma (GBM)) and the formation of fibrotic scars led to
improved survival of mice in preclinical trials.
GBM is both the most common brain cancer and the most
aggressive, with a five-year survival rate of less than 5%. Even
with treatment, more than 90% of patients have their tumors recur.
In this study, "Fibrotic Response to Anti-CSF-1R Therapy
Potentiates Glioblastoma Recurrence," Professor Joyce and her team
sought to understand the mechanisms behind GBM recurrence and how
to improve existing therapies.
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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