Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Common molecule notifies immune system of prostate cancer

14.01.2008
In experiments with mice, researchers have found that the body’s immune system can use a surprisingly common molecule to recognize prostate tumors. The molecule comes from a protein found in all cells of the body; however, immune cells appear to respond to it only when it is present on the surface of cells within a tumor.

Understanding how this protein, known as histone H4, signals the immune system to respond to malignant cells may help researchers refine immunotherapy strategies that harness the body's own immune system to fight tumors. Some types of immunotherapy are already being tested in patients, but many questions remain unanswered. In particular, researchers want to know if tumor cells display molecular signposts that tell the immune system, “I'm a cancer cell, destroy me.”

Howard Hughes Medical Institute investigator James P. Allison and his team report finding one such signpost in prostate tumors in mice. The finding points toward possible improvements in immunotherapy.

“We know very little about how the immune system responds to tumors, especially early tumors,” said Allison, director of the Ludwig Center for Cancer Immunotherapy at Memorial Sloan-Kettering Cancer Center in New York. “Is the tumor at that stage invisible, or can immune cells detect it? And if they can detect it, can they mount a response? Those are the two big questions.”

Allison's research, published in the January 11, 2008, issue of Science, found that immune cells can, in fact, detect prostate cancer, at least in lab mice. However, the immune system mounts only a feeble attack against the tumor.

But the signpost Allison's team identified might make revving up that feeble response much easier.

The strategy relies on a specific type of immune system cell called a killer T cell. Each of these cells bristles with thousands of receptors that recognize molecules that do not belong in the body. When a T cell recognizes a foreign molecule, it tries to destroy the cell carrying it. The T cell then replicates, making copies that also latch onto the same foreign molecule.

In 1982, while at the University of Texas at Austin, Allison discovered T cell antigen receptors, the fork-like proteins that recognize the molecular signals on invading cells. Each T cell has a different receptor as determined by genetics and a random process. There are trillions of different T cell receptors possible, a number greater than the number of cells in the human body.

In normal tissue, the distribution of receptors found on T cells is random. That is, a batch of T cells will have a range of receptors, with none being more common than the others.

But in the new work, one of Allison's colleagues, Peter Savage, discovered that the cancerous prostate glands of mice harbored many T cells carrying a specific receptor. That meant that a single T cell had recognized the malignancy and had replicated.

Savage found the overrepresented receptor in 15 of 20 mice with prostate cancer. “That told us something was going on,” said Allison. “You don't see this in normal mice.”

At this point, the team knew that the immune system of the mice was recognizing a particular signpost of malignancy. But they had no idea what the signpost was.

“The obvious question was, ‘What are these T cells seeing?’” said Allison. “And that's when the hard work started.”

The team chopped up tumor cells in a dish and mixed them with antigen presenting cells and T cells carrying the receptor they had identified. The T cells switched on, which “showed we had really gotten the right receptor,” said Allison. However, during control experiments, the team also found that nearly any type of tissue, if it was chopped up, would activate the T cells.

“This started some head scratching,” said Allison. Because if every tissue activated the T cells, it meant that the signpost was not specific to the cancer cells.

The mystery deepened when mice were engineered to produce T cells that carried only the receptor of interest. Those cells did not attack every tissue. They only attacked – albeit feebly – the prostate tumors. It was a conundrum.

Returning to their experiments in the lab dish, the team decided to focus on specific parts of the tumor cells. They soon discovered that only molecules from the nucleus activated their T cells.

“This was really a surprise, because normally, nuclear proteins don't get fed onto the cell surface,” said Allison. And in living animals, T cells only recognize molecules on the surface of other cells – they can't peer deep into the nucleus.

The team then searched for particular nuclear proteins that activated the T cells. They eventually struck on histone H4. As the wrapper that sheaths the DNA inside all cells, histones are abundant in the nucleus. The finding explained why the normal cells, when chopped up, had activated the T cells – their histones were being exposed.

The team had identified the molecular signpost that activated the T cells, but they had also landed on another big question – how do the histones rise to the surface of the tumor cells. “Every cell has a ton of histone, and we just don't know why the tumor cells put it on their surface,” said Allison.

The team is now examining the blood of patients with prostate and other cancers to see if people, like mice, carry T cells sensitive to histone. If so, “then we can take those cells out and try to activate them,” said Allison. “Those cells already recognize the tumor. If we can mobilize them, maybe it will have a therapeutic effect.”

Allison and his colleagues are also conducting studies to determine whether the presence of histone H4-reactive T cells in the blood could be used as a diagnostic marker for the early detection of prostate cancer.

Jennifer Michalowski | EurekAlert!
Further information:
http://www.hhmi.org

More articles from Health and Medicine:

nachricht Tracking movement of immune cells identifies key first steps in inflammatory arthritis
23.01.2017 | Massachusetts General Hospital

nachricht Team discovers how bacteria exploit a chink in the body's armor
20.01.2017 | University of Illinois at Urbana-Champaign

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: Quantum optical sensor for the first time tested in space – with a laser system from Berlin

For the first time ever, a cloud of ultra-cold atoms has been successfully created in space on board of a sounding rocket. The MAIUS mission demonstrates that quantum optical sensors can be operated even in harsh environments like space – a prerequi-site for finding answers to the most challenging questions of fundamental physics and an important innovation driver for everyday applications.

According to Albert Einstein's Equivalence Principle, all bodies are accelerated at the same rate by the Earth's gravity, regardless of their properties. This...

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Tracking movement of immune cells identifies key first steps in inflammatory arthritis

23.01.2017 | Health and Medicine

Electrocatalysis can advance green transition

23.01.2017 | Physics and Astronomy

New technology for mass-production of complex molded composite components

23.01.2017 | Process Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>