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 Transport of molecular motors into cilia
28.03.2017 | Aarhus University

nachricht Asian dust providing key nutrients for California's giant sequoias
28.03.2017 | University of California - Riverside

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A Challenging European Research Project to Develop New Tiny Microscopes

The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.

To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Researchers shoot for success with simulations of laser pulse-material interactions

29.03.2017 | Materials Sciences

Igniting a solar flare in the corona with lower-atmosphere kindling

29.03.2017 | Physics and Astronomy

As sea level rises, much of Honolulu and Waikiki vulnerable to groundwater inundation

29.03.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>