Image of human breast cancer cells showing A) immunosuppressive macrophages near tumor connective tissue, and B) immunostimulatory macrophages near tumor nests. Credit: Nir Ben Chetrit.
Key Points:
- A new method can illuminate the activities of cells throughout an organ or a tumor at unprecedented resolution.
- This method allows the mapping of spatial organization of tissues, including cell types, cell activities and cell-to-cell interactions
- Details of the tumor immune environment could inform scientists on ways to design future immunotherapies.
Researchers at Weill Cornell Medicine, NewYork-Presbyterian and the New York Genome Center have shown that a new method can illuminate the identities and activities of cells throughout an organ or a tumor at unprecedented resolution.
The method, published in Nature Biotechnology, records gene activity patterns and the presence of key proteins in cells across tissue samples, and can retain information about the cells’ precise locations. This enables the creation of complex, data-rich “maps” of organs, including diseased organs and tumors, which could be widely useful in basic and clinical research.
“This technology is exciting because it allows us to map the spatial organization of tissues, including cell types, cell activities and cell-to-cell interactions, as never before,” said study co-senior author Dan Landau, an associate professor of medicine in the Division of Hematology and Medical Oncology.
The method, called Spatial PrOtein and Transcriptome Sequencing (SPOTS), is based in part on existing 10x Genomics technology. It uses glass slides normally found in microscope-based pathology for imaging tissue samples, but coated with thousands of special probe molecules. Each of the probe molecules contains a molecular “barcode” denoting its two-dimensional position on the slide. Once the thinly sliced tissue sample is placed on the slide, the probe molecules on the slide grab adjacent cells’ messenger RNAs (mRNAs).
In the study, the researchers demonstrated SPOTS on tissue from a normal mouse spleen, revealing the complex functional architecture of this organ including clusters of different cell types, their functional states, and how those states varied with the cells’ locations. The team also mapped the cellular organization of a mouse breast tumor. The results showed immune cells in two states—one active and tumor-fighting, the other immune-suppressive and forming a barrier to protect the tumor.
Such details of the tumor immune environment might help explain why some patients respond to immune-boosting therapy and some don’t, and thus could inform the design of future immunotherapies.
Researchers hope to narrow down the methods’ resolution to single cells, while adding other layers of key cellular information.