A recent study from Washington University School of Medicine in St. Louis has created detailed three-dimensional (3D) maps of various tumor types. These cancer atlases illustrate how tumor cells and their surrounding environments are organized and how this organization changes when tumors spread to other organs.
The findings could provide scientists with essential blueprints for tumors, potentially leading to innovative therapies and advancing cancer biology, researchers say.
This study is part of a collection of 12 papers published on October 30 in the Nature suite of journals. These papers come from the Human Tumor Atlas Network, a research group funded by the National Cancer Institute (NCI) of the National Institutes of Health (NIH). The 3D analysis, published in Nature, focuses on cancers of the breast, colon, pancreas, kidney, uterus, and bile duct.
Over the past decade, cancer research has significantly improved our understanding of cellular activities within tumors, including the behavior of both cancerous and supportive cells at the single-cell level. This new study not only highlights the roles of individual cells but also their locations within intact tumors and how they interact with nearby cells.
This information could help scientists understand tumor spread and the development of treatment resistance.
“These 3D maps of tumors are crucial because they finally allow us to visualize what we have only been able to infer about tumor structures and their complexity,” said Dr. Li Ding, co-senior author of the study and a member of the Siteman Cancer Center at Barnes-Jewish Hospital and WashU Medicine.
The researchers discovered that tumors generally show higher metabolic activity at their cores and increased immune system activity at their edges. They also found that tumors can contain multiple regions with different genetic mutations influencing growth. This insight suggests that varying targeted treatments may be necessary to address critical mutations in different tumor regions.
“This understanding of 3D cancer metabolism will impact how our current treatments work—or don’t work—and will lead to new cancer therapies,” said Dr. Ryan C. Fields, another co-senior author and a physician at Siteman.
The research identified regions within tumors with high immune cell activity, known as “hot regions,” and others with minimal immune activity, referred to as “cold regions.” Hot regions typically respond well to immunotherapies, while cold regions do not. This distinction helps explain why some tumors initially respond to immunotherapy but later develop resistance. Identifying various mutation profiles and the characteristics of hot and cold regions could allow for the creation of effective treatment strategies for all tumor neighborhoods.
The study’s co-first authors, graduate students Chia-Kuei (Simon) Mo and Jingxian (Clara) Liu, noted significant variations in how deeply immune cells infiltrated different tumors and where specific immune cell types, such as T cells and macrophages, gathered. Some metastatic samples showed cancer cells breaching immune boundaries, which could illustrate “immune cell exhaustion.” This condition occurs when the immune system becomes overwhelmed by aggressive cancer, leading to uncontrolled growth.
“If we can identify exhausted T cells within a tumor, we might activate them using checkpoint inhibitors or other immunotherapies,” Ding explained. “If we don’t find them, we can infer that certain immunotherapies may not be effective. These tumor maps allow us to predict treatment resistance, a capability we have not had before.”
In addition to the 3D tumor analysis, WashU Medicine researchers led two additional studies within this publication package. One study, co-led by Ding and Dr. William E. Gillanders, focuses on breast cancer and how different types of breast tumors originate from various cell types. The team found T cell exhaustion to be common in aggressive triple-negative breast cancer, providing insight into treatment strategies based on the tumor’s cellular origins and immune landscape.
Another study describes new methods for conducting 3D analyses of tumors, co-led by Ding and Dr. Benjamin J. Raphael from Princeton University.
This research was supported by the National Institutes of Health (NIH) and the Damon Runyon Cancer Research Foundation. The studies are expected to make significant contributions to understanding tumor evolution and microenvironment interactions, paving the way for more effective cancer treatments.
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