Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

How T cells attack tumors

21.02.2007
Our immune system struggles to eliminate tumors effectively. By unraveling its strategies, we can enhance its effects on tumor cells and so improve the clinical prospects of cancer immunotherapy. At the Institut Curie, Inserm and CNRS researchers have for the first time used two-photon microscopy in real-time in vivo studies to show how T cells infiltrate a solid tumor.

These “defenders”, methodically surround enemy positions and “patrol” until they encounter a tumor cell, which they have previously learned to recognize. They eliminate the tumor cell, and then resume their rounds. Fast movements of the T cells signal either the absence of the adversary, or the defeat of the enemy on the battlefield. These findings are published in The Journal of Experimental Medicine.

Institut Curie researchers have just filmed how T cells destroy a tumor. The original images have been assembled into twelve video sequences, through a close collaboration between an expert in two-photon microscopy, Luc Fetler, who is an Inserm researcher in the CNRS/Institut Curie Physical Chemistry Unit(1), and immunologists, notably Alexandre Boissonnas in the Inserm Immunity and Cancer Unit(2) at the Institut Curie.

Our body’s defense against infection or a tumor is based on the involvement of a host of components with general or highly specialized tasks. Cytotoxic T cells fall into the latter category. At their surface they have a membrane receptor complementary to the antigen of the tumor cells that are to be eliminated. Alerted by the presence of this antigen, the T cells are activated, and then identify and bind to infectious or tumor cells, before delivering into them a fatal load of enzymes.

... more about:
»Antigen »T cells »micrometers »tumor cells

When T cells infiltrate a tumor

Before Alexandre Boissonnas and Luc Fetler did this work, no one had observed on a cellular scale what happens when activated T cells arrive in a solid tumor. Their original experimental model sheds light on the strategy adopted by T cells to destroy the tumor.

Recognition of the tumor antigen determines the behavior of T cells. This conclusion emerged from the researchers’ observation in mice of the movements of T cells, in tumors with an antigen, ovalbumin, and in control antigen-free tumors. Tumor cells, with or without antigen, were inoculated into mice, and eight to ten days later, when the tumors had grown to a volume of 500 to 1000 mm3, the mice were injected with a large number of T cells specific for the antigen OVA.

As expected, only the antigen-bearing tumor was eliminated, after one week. In the meantime, a two-photon microscope (see box) was used to watch what happened in the first 150 micrometers of the tumor. Each shot revealed different cell populations, blood vessels, and collagen fibers, and by stitching together several successive images, it was possible to reconstitute the trajectory of a T cell.

The researchers examined the T cells and tumor cells at two distinct periods of tumor growth. In the antigen-free tumor, the T cells ceaselessly patrolled at high speed (about 10 micrometers per minute), whatever the stage of tumor growth. In the antigen-bearing tumor, on the other hand, T cell behavior varied: when the tumor stopped growing, three to four days after the injection of lymphocytes, the T cells patrolled slowly (4 micrometers per minute), and frequently stopped. Their mean speed plateaued at 4 micrometers per minute. Later, when the tumor regressed, most T cells resumed fast movements.

The trajectories of T cells are confined to the dense zones of living tumor cells, but are more extensive and varied in regions littered with dead tumor cells. The Institut Curie researchers conclude that the presence of the antigen stops the T cells, which are busily recognizing and killing the enemy.

When analyzing their distribution in each tumor, the researchers always found T cells at the periphery, but deep penetration, and hence effective elimination of the tumor, was contingent on the presence of the antigen. These findings were validated with two types of experimental tumors, generated by two lines of cancer cells. It is now up to clinicians to verify whether deep penetration of T cells is a criterion of good prognosis.

To optimize immunotherapy, one of the most promising approaches to cancer treatment, we need a better grasp of how the immune system works. The Institut Curie has for many years participated actively in the development of innovative strategies in this regard. Two clinical trials are presently under way at the Institut Curie, one in patients with choroid melanoma and the other in cervical cancer patients.

Catherine Goupillon | alfa
Further information:
http://www.jem.org/

Further reports about: Antigen T cells micrometers tumor cells

More articles from Life Sciences:

nachricht Bolstering fat cells offers potential new leukemia treatment
17.10.2017 | McMaster University

nachricht Ocean atmosphere rife with microbes
17.10.2017 | King Abdullah University of Science & Technology (KAUST)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Ocean atmosphere rife with microbes

17.10.2017 | Life Sciences

Neutrons observe vitamin B6-dependent enzyme activity useful for drug development

17.10.2017 | Life Sciences

NASA finds newly formed tropical storm lan over open waters

17.10.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>