Navigation Links
Innovative movies show real-time immune-cell activity within tumors

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.

Insights from this new view of the body's on-board defenses against cancer may open the way for improved immunotherapies to treat the disease.

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?

"In the animals that received the vaccination, we saw two waves of activity after the T cells entered the tumor microenvironment," Weninger says. "Early on, the T cells didn't actively migrate through the tissue. This, we found, was because they were interacting directly with the tumor cells in place. In several instances, we were actually able to see the tumor cells dying ?the first time that has ever been observed in real-time in living animals. Then, once the tumor cells had been destroyed, we saw a dramatic change in the behavior of the activated T cells. They began to migrate actively, searching for any other tumor cells that might remain in the area."

In contrast, in the mice that did not receive the vaccination, the T cells were much sparser and, importantly, distinctly inactive in their migration. Consequently, tumor cell death was very rare under these conditions.

The researchers then designed a second set of experiments to complement the first. In the first set of experiments, the T cells were varied in two groups of mice while the target tumor cells were uniform. In the second set, the T cells were uniform while the tumor cells varied in two groups of mice according to whether or not they presented a specific antigen to which the T cells would respond.

T cells were removed from mice without tumors, activated in the test tube, and then reintroduced into mice carrying tumors that either did or did not express the antigen. This procedure, referred to as adoptive transfer, is an immunotherapy strategy against cancer being tested in a number of human clinical trials. In some of those trials, a patient's own T cells are removed, tested for their ability to recognize the patient's cancer cells, activated and expa nded greatly in numbers in the laboratory, and then returned to the patient.

The hope in these trials is that these enhanced T cell populations will specifically target and destroy the patient's cancer. To date, despite a few remarkable successes, these trials have proven frustratingly uneven. Greater insights into the mechanisms of interaction between T cells and tumor cells could provide vital new information to advance these efforts.

"Through adoptive transfer," Weninger explains, "we were able to compare two situations, one in which the T cells recognize something on the tumor and one in which they don't. When the T cells recognized the antigen, they interacted directly with the tumor cells. After tumor cell destruction, they became actively migratory, hunting for more tumor cells. In the absence of antigen, the T cells did not interact with tumor cells, and could not sustain an active migratory behavior within tumors."

"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."


Source:The Wistar Institute

Related biology news :

1. Innovative collaboration brings Arctic science into the classroom
2. Innovative coating could give medical implants a longer life
3. Innovative method for creating a human cytomegalovirus vaccine outlined
4. Ultrasound upgrade produces images that work like 3-D movies
5. First real-time view of developing neurons reveals surprises, say Stanford researchers
6. LUCA technologies confirms real-time methane generation
7. Molecule by molecule, new assay shows real-time gene activity
8. Hopkins researchers develop new tool to watch real-time chemical activity in cells
9. Novel system developed to turn data into real-time, interactive 3-D images
10. Exercise training in ordinary people affects the activity of 500 genes
11. New bioinformatics technique for systematically analyzing key regions in DNA that help control gene activity
Post Your Comments:

(Date:11/17/2015)... Mass. , Nov. 17, 2015 Pressure ... leader in the development and sale of broadly enabling, ... worldwide life sciences industry, today announced it has received ... its $5 million Private Placement (the "Offering"), increasing the ... $4,025,000.  One or more additional closings are expected in ...
(Date:11/12/2015)... 2015  A golden retriever that stayed healthy despite ... has provided a new lead for treating this muscle-wasting ... Institute of MIT and Harvard and the University of ... Cell, pinpoints a protective gene that ... effects. The Boston Children,s lab of Lou Kunkel ...
(Date:11/12/2015)...   Growing need for low-cost, easy to ... paving the way for use of biochemical sensors ... in clinical, agricultural, environmental, food and defense applications. ... medical applications, however, their adoption is increasing in ... emphasis on improving product quality and growing need ...
Breaking Biology News(10 mins):
(Date:11/30/2015)... , December 1, 2015 Partnership includes an ... for the u niversity , ... support treatment s cale - up ... (ARVs)   Africa , where licensees based anywhere in the ... on SDN technology. --> Africa , where licensees based anywhere ...
(Date:11/30/2015)... Mass. , Nov. 30, 2015 ... HART ), a biotechnology company developing bioengineered organ ... received written notification from The NASDAQ Stock Market ... bid price requirements. The letter noted that as ... HART,s common stock having exceeded $1.00 per share ...
(Date:11/30/2015)... BETHESDA, Md. , Nov. 30, 2015 /PRNewswire/ ... property development company committed to the fostering and ... on the current and prospective initiatives designed to ... , Chief Executive Officer of Spherix. "Based on ... potential future licensees exceeds $50 billion and Spherix ...
(Date:11/30/2015)... 30, 2015  Champions Oncology, Inc. (CSBR), engaged in ... personalize the development and use of oncology drugs, today ... will be presenting at the LD MICRO Investor Conference ... Time (PST).  The conference, held at the Luxe Sunset ... , will feature 200 small/micro-cap companies and is ...
Breaking Biology Technology: