Brain metastases are the most common form of brain cancer, occurring almost ten times more often than cancers that start in the brain. While treatment options for brain metastases have improved in recent years, much remains to be understood about metastasis formation.
The team combined high-level single-cell analyzes of human brain tissue metastases from different cancer types and experimental models to identify and understand tumor-specific recurrence patterns. metastases in patients.
They also identified a comparable metastatic niche or microenvironment and an immunosuppressive stromal enriched with metastasis-associated T cells and macrophages that appeared to play a role in the dynamics. of two prototypes.
“These archetypes coexist in each metastatic tumor,” said Gonzalez. “As for non-proliferating MTCs, these cells are reprogrammed to express genes that cause inflammation, stress, and other altered conditions. These immune interactions with the tumor can shape the state of being.” of the MTC.”
“Zena Werb was the first to see the potential and feasibility of capturing human metastases and combining them with cutting-edge technologies such as single-cell transcription and CyTOF,” said Gonzalez.
“She believes that by analyzing human brain metastases, we can determine the relationship between these cellular processes regulated by the MTC and their specific processes.
micro environment. “Werb, a world-renowned researcher in cancer biology and associate director of basic science at the UCSF Helen Diller Comprehensive Family Cancer Center, has transformed the field by emphasizing the important role we play. The importance of local “neighborhoods” of cells in determining tumor growth and behavior.
More than four decades; Her work laid the foundations for the development of immunotherapy and other modern cancer treatments. Werb passed away in 2020 at the age of 75, but her legacy lives on with her colleagues, whom she mentored.
“She believed in this project from the very beginning and encouraged me to persevere even when the collection and handling of these rare specimens was quite difficult,” says Gonzalez.
“Zena also helped organize a fruitful collaboration with UCSF colleagues Joanna Phillips, MD, Ph.D., and Matthew Spitzer, Ph.D., who played a key role in this major project. “
Roose added that Gonzalez’s work forms an important foundation for the team’s collaborative effort with the UCSF Endeavor program to better understand how metastasis occurs when cancer cells interact with surrounding host cells. around the tumor.
Roose found it extremely rewarding to meet Hugo through the site of this brain metastasis project. “I could just see Zena walk into my office, give us a thumbs up and give us a tight hug,” Roose said.