Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists Identify Cell Defects that Limit Immune System’s Impact on Late-Stage Tumors

22.01.2004


Although vaccines developed to help the immune system fight tumors appear to have an impact against early-stage tumors, they have little if any success in slowing the growth of tumors in later stages. Now researchers writing in the Feb. 1, 2004 issue of The Journal of Immunology identify abnormalities in the immune system’s T cells, provide insight into their origin, and describe how these defects can be prevented and "repaired" in animal experiments.

"Conventional thinking and previous studies suggest that the tumor environment is responsible for immune dysfunction in cancer-fighting T lymphocytes that congregate at the site of a tumor. The major unresolved question is the origin and mechanism responsible for immune dysfunction in tumor-infiltrating T cells. We found that damaged T cells arose from a particular cell lineage, within a tumor environment that lacks factors promoting their survival," said Keith L. Black, MD, director of Cedars-Sinai’s Maxine Dunitz Neurosurgical Institute, where the mouse studies were conducted. "Furthermore, we were able to influence the cells in a way that decreased the number of dysfunctional cells, a finding that we hope may eventually lead to more effective vaccine therapies against established tumors."

In a localized immune response, T cells are mobilized to attack cells that the immune system recognizes as invaders. Because specific lymphocytes recognize and attack specific immune threats, they are called "antigen-specific." In cancer vaccine experiments, such as those ongoing at the Institute to improve treatment for brain tumors, researchers seek to improve the immune response by helping cancer-fighting cells identify tumor cells as potential targets.



T cell activation is considered a major defense mechanism in the prevention of tumor formation, and in rodent studies T cell responses have been able to eradicate recently established tumors. In both humans and animals, however, T cell mobilization appears to have little effect when directed against advanced tumors.

While many types of T lymphocytes exist, differentiated by their molecular makeup and the roles they play, CD4 and CD8 cells are considered the "normal population" responding to threatening antigens. But in these studies, most T cells present within the tumors were "double-negative," expressing neither CD4 nor CD8, but instead exhibiting abnormal characteristics.

"While most studies assign T cell defectiveness and death to the tumor environment, we now know more about the kinds of T cells that are susceptible and how they become defective. This allowed us to target novel properties to prevent or reverse the defects," said Christopher J. Wheeler, PhD, research scientist and the paper’s senior author. "The T cell defects could be incurred independent of their reactivity to the tumor per se, and on a general level involved signals for survival."

T cells normally receive "survival" signals provided by signaling molecules or certain hormones. In the absence of these survival signals, the cells simply die by default.

"These signals are usually available in the body but they evidently are not available to T cells in tumors," said Dr. Wheeler. "We conducted an experiment to test this observation, adding back the molecules that can induce such signals, and we found a reduction in the abnormal T cells."

The recent research also provides new insight into another aspect of the relationship between tumors and defective T cells. Because those T cells responding to a tumor are believed to be specifically reactive to that tumor antigen, it has been assumed - perhaps incorrectly - that the T cell defects were in some way related to antigen-specificity and reactivity.

"We placed non-activated and non-tumor-specific T cells into tumors and found that they readily became defective. This runs counter to the predominant paradigm holding that defectiveness is related to antigen reactivity or specificity. At least experimentally, this is not the case. Of course, in a real tumor, most of the T cells that are present are going to be antigen-specific. Antigen-specificity allows T cells to infiltrate tumors, but this is not necessarily involved in their defectiveness," Dr. Wheeler said.

If the findings in this series of experiments are supported through additional studies and their implications in animals are consistent in humans, they may help researchers devise more effective approaches to immunotherapy. Theoretically, at least, the vaccine would "turn on" the immune system and focus it on the tumor while the promotion of survival signals into the tumor would "repair" defective T cells to help them stay alive to fight.

Cedars-Sinai is one of the largest nonprofit academic medical centers in the Western United States. For the fifth straight two-year period, it has been named Southern California’s gold standard in health care in an independent survey. Cedars-Sinai is internationally renowned for its diagnostic and treatment capabilities and its broad spectrum of programs and services, as well as breakthroughs in biomedical research and superlative medical education. It ranks among the top 10 non-university hospitals in the nation for its research activities.

Citation: The Journal of Immunology, February 1, 2004: "Characterization of
Defective CD4-CD8- T cells in Murine Tumors Generated Independent of Antigen
Specificity."

Sandra Van | Cedars-Sinai Media Relations
Further information:
http://www.csmc.edu

More articles from Health and Medicine:

nachricht Hot cars can hit deadly temperatures in as little as one hour
24.05.2018 | Arizona State University

nachricht 3D images of cancer cells in the body: Medical physicists from Halle present new method
16.05.2018 | Martin-Luther-Universität Halle-Wittenberg

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Powerful IT security for the car of the future – research alliance develops new approaches

The more electronics steer, accelerate and brake cars, the more important it is to protect them against cyber-attacks. That is why 15 partners from industry and academia will work together over the next three years on new approaches to IT security in self-driving cars. The joint project goes by the name Security For Connected, Autonomous Cars (SecForCARs) and has funding of €7.2 million from the German Federal Ministry of Education and Research. Infineon is leading the project.

Vehicles already offer diverse communication interfaces and more and more automated functions, such as distance and lane-keeping assist systems. At the same...

Im Focus: Molecular switch will facilitate the development of pioneering electro-optical devices

A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.

The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

In focus: Climate adapted plants

25.05.2018 | Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

 
Latest News

In focus: Climate adapted plants

25.05.2018 | Event News

Flow probes from the 3D printer

25.05.2018 | Machine Engineering

Less is more? Gene switch for healthy aging found

25.05.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>