Dr. Wolfgang Weninger and his team of researchers at the Wistar Institute have used a “two-photon microscope” to capture real time video of immune cells attacking cancerous cells.
Using advanced new microscopy techniques in concert with sophisticated transgenic technologies, scientists at The Wistar Institute have for the first time created three-dimensional, time-lapse movies showing immune cells targeting cancer cells in live tumor tissues. In recorded experiments, immune cells called T cells can be seen actively migrating though tissues, making direct contact with tumor cells, and killing them.
With a series of movies made under different experimental conditions, the researchers resolved important questions about the mechanisms by which T cells act against cancer. Their findings, published online November 20, will appear in the November 27 print edition of The Journal of Experimental Medicine.
“We’ve taken the first real-time look at the final phase of the immune system’s response to cancer cells,” says Wolfgang Weninger, M.D., an assistant professor in the Immunology Program at Wistar and senior author on the new study. “This has enabled us to delineate the rules of T cell migration and engagement directly within the intricate microenvironment of tumors.”
The scientists used a leading-edge instrument called a two-photon microscope, able to peer inside living tissues. The microscope tracked and recorded the movements in three dimensions over time of T cells in a transgenic mouse developed by Weninger and Ulrich von Andrian at Harvard Medical School in which the cells fluoresce green. In addition, for this study, tumor cells in the mice were engineered to fluoresce blue.
In one group of the mice, a vaccine developed by Wistar professor and study co-author Hildegund C.J. Ertl, M.D., was used to activate the T cells that recognize a molecule on the surface of the tumor cells. Such molecules are referred to by immunologists as antigens. In a second group, no such vaccine was given.
Movies captured with the two-photon microscope then recorded the unfolding scene in the so-called tumor microenvironment. How would the green T cells behave in the two groups of mice?
“There are several significant conclusions from these experiments,” Weninger says. “First, it is now possible to visualize the behavior of the individual cellular components of the tumor microenvironment in real-time. Second, we have demonstrated that T cells physically interact with tumor cells, which had not been shown before. Finally, it’s the presence of antigen that determines how T cells migrate and interact with the tumor cells.
“These experiments set the basis for unraveling the molecular requirements for T cell migration and T cell-tumor cell interactions. We should then be able to use results from this research to further improve immunotherapeutic strategies against cancer in patients.”
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