Study Enabled by 10x Genomics Single Cell and Spatial Technologies Explains Why Immunotherapy is More Effective for Certain Brain Tumors Than Others
- Immune checkpoint blockade is more effective for treating cancers that spread to the brain than for cancers that originate in the brain
- Brain metastases had higher T-cell infiltration into the tumor parenchyma
- Identified immune subpopulation correlated with better overall survival
- New combination immunotherapy strategies using blocking inhibitory receptors
- None.
Researchers uncover mechanisms behind divergent responses to immune checkpoint blockade between primary and metastatic brain tumors
Researchers conducting the study, "Immune checkpoint blockade induces distinct alterations in the microenvironment of primary and metastatic brain tumors," analyzed resected glioblastoma and brain metastases from patients prior to immunotherapy and after with Chromium Single Cell Immune Profiling and Visium Spatial Gene Expression. Spatial transcriptomics revealed that brain metastases had higher T-cell infiltration into the tumor parenchyma, potentially because T-cells have already been primed in the draining lymph nodes by tumor antigens from extracranial tumors. Such priming may not occur for primary brain tumors, like glioblastoma.
Researchers also found an immune subpopulation in both tumor types that was correlated with better overall survival. This population can be rejuvenated by blocking inhibitory CTLA-4 and TIGIT receptors, suggesting new combination immunotherapy strategies that are now being investigated in phase 1 trials by the group.
"Single cell RNA-seq and spatial transcriptomics technologies were integral to this study. In particular, we used single cell RNA-seq to identify the transcriptional program of distinct T cell sub-populations that infiltrated these tumors and how these programs changed with immunotherapy," said the study's senior author, Robert Prins, a professor of molecular and medical pharmacology and of neurosurgery at the David Geffen School of Medicine at UCLA. "Spatial transcriptomics was used to overlay many of the gene signatures specific to the immune subsets and highlight how there were distinct changes in the spatial architecture following immunotherapy."
"This study is the latest in more than 1,200 peer-reviewed publications that use 10x Genomics' tools to advance our understanding of cancer," said Ben Hindson, Co-founder and Chief Scientific Officer at 10x Genomics. "We're so proud to have our technologies help researchers make new discoveries like these, which help transform our understanding of health and disease and open up new and better ways to diagnose, treat and ultimately cure cancer."
This study is the latest development resulting from a partnership between 10x Genomics and the Parker Institute for Cancer Immunotherapy (PICI). The collaboration began in 2021 with the goal to accelerate the pace of research in immuno-oncology by promoting joint effort research using 10x Genomics' tools.
Since the start of the partnership, 10x and PICI have initiated multiple scientific collaborations focused on enabling the use of single cell, spatial transcriptomics and in situ technologies to detangle mechanisms of response and resistance to immunotherapies, like checkpoint inhibitors and CAR-T therapies. They also worked together on a scientific workshop that was summarized in Nature Medicine in 2022.
John Connolly, PhD, Chief Scientific Officer of PICI, said findings from the UCLA-led study illuminate the factors shaping patient responses to immunotherapy and provide valuable insights for refining innovative strategies to transform the landscape of brain tumor treatment.
"By partnering with 10x Genomics, UCLA and others, we are working to accelerate breakthrough immune therapies for patients," Connolly said. "This research exemplifies the value of scientific collaboration and our dedication to addressing the challenges of brain tumors, one of the most formidable tumor types."
For more information, please read this article from UCLA Health.
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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