Sur la piste d'un vaccin contre le cancer

Les chercheurs à l'université de Stanford ont commencé à jeter de la lumière sur la raison qui empêche le système immunitaire de stopper de tels cancers comme le cancer de la le mélanome et ont suggérer que ces découvertes pourraient paver la voie à de meilleurs traitements pour cette maladie.

Dans la petite étude, les scientifiques ont trouvé que les cellules du système immunitaire pour une majorité de gens ne répondaient pas proprement à la molécule appelé interféron qui normalement active le système immunitaire. Sans la capacité de répondre à l'interféron, les cellules sont bien sûr moins capables de se défendre du cancer.

Ces résultats expliquent une décennie de recherches qui montre que les gens avec le cancer ont souvent des systèmes immunitaires déficients. Jusqu'à maintenant, les chercheurs pouvaient dire que le système immunitaire ne fonctionnait pas correctement mais ils ne pouvaient pas dire quels gènes ou quels chemins cellulaires étaient impliqués. Le fait de trouver cette interruption dans la réponse à l'interféron pourrait aider à développer un vaccin pour traiter les cancers. " Nous pensons que c'est un chemin majeur par lequel la malfonction du système immunitaire arrive chez les gens." dit Peter Lee.

The group started by separating out the four major types of immune cells from people with melanoma and from healthy people. These cells were B cells, two types of T cells and NK, or natural killer, cells. Then, postdoctoral scholar Rebecca Critchley-Thorne, PhD, lead author of the paper, looked in the immune cells of healthy people vs. those with melanoma to see if they had the same levels of activation of roughly 20,000 genes.
She found that the B cells and both types of T cells in people with melanoma showed activity levels that differed from healthy people in only 25 of those genes. Seventeen of those 25 were normally turned on in response to interferon.
"Interferon normally acts as a critical signal in activating immune cells," said Critchley-Thorne. Without the ability to respond to interferon, those cells might detect the cancer but won't activate properly.
This type of experiment only shows that certain genes are turned on at different levels in people with melanoma. It doesn't prove that the cells behave differently than the immune cells of normal people. To verify that the interferon signaling was defective in people with melanoma, Critchley-Thorne isolated those cells and exposed them to interferon.
As predicted, immune cells from people with melanoma also failed to respond normally to the immune activation signal. However, she found that if she left the cells in the presence of a high dose of interferon for much longer than would normally be required, those cells did begin responding.
Lee said the finding explains why a common melanoma treatment, in which some doctors have treated patients with prolonged exposure to interferon, sometimes helps. "Doctors knew it worked in some people but didn't know why," Lee said. This data suggests that treatment works by overcoming the immune system's inability to react properly to interferon.
If Lee's suspicion turns out to be true, doctors may be able to screen melanoma patients for interferon response and provide prolonged interferon treatment for only those patients whose immune cells have defects in that pathway. That means patients who wouldn't benefit from the treatment could avoid suffering through interferon's flu-like side effects.
The work was funded by the National Institutes of Health. Other Stanford researchers who contributed to the work include postdoctoral scholars Ning Yan, PhD, and Serban Nacu, PhD; and Susan Holmes, PhD, professor of statistics.

Jun. 11, 2008) — Researchers from the Tubingen University, Department of Dermatology, uncovered an entirely new understanding on how the immune system may control tumor development. Until now it is strongly believed that the immune system controls growth of tumors by killing tumor cells.

Des chercheurs ont découvert une nouvelle manièer de comprendre comment le système immunitaire controle le développement des tumeurs. jusqu'à maintenant on croyait fermement que le système immunitaire controlait le développement de la tumeur en la tuant.

The Tubingen researchers, members of the Comprehensive Cancer Center, now show that immune responses can prevent tumor growth without killing tumor cells.

Maintenant ces chercheurs expliquent que le système immunitaier peut prévenir la croissance de la tumeur sans la tuer.

They used a model of endogenously growing tumors that develop, like many human tumors, because of a defect in normal cell death. The researchers show that the immune system can prevent tumor growth without destroying tumor cells. They show that early treatment of developing tumors arrests tumor development at very early stages through a strictly cytokine mediated mechanism. One of the important players that prevents the outgrowth of malignant tumors is interferon.

L'un des joueurs important pour arrêter le développement est l'interféron.

The researchers show further a second important aspect: Immune responses can both - either induce tumor dormancy or, unexpectedly, tumor growth. In the absence of either interferon or tumor necrosis factor the immune response converts the from a protective into a tumor promoting immune response.

Les chercheurs montrent aussi un aspect important : le système immunitaire peur ou faire entre la tumeur en état de coma ou faire croitre la tumeur. En l'Absence d'interféron ou d'un aure agent de nécrose de la tumeur, le système immunitaire se convertir en promoteur de la tumeur.

In conclusion, the paper (published in Cancer Cell, 10.6.2008) gives a great hope and new aspects for the development of new tumor vaccines. They show that tumor immune responses can induce tumor dormancy, which means that the immune response arrests tumors at early stages.

En conclusion, l'Article publié dans Cancer Cell donne un grand espoir pour le développement de vaccins.

Yet, these immune responses have to occur early in tumor development and have to provide the correct pattern of cytokines. In the case of an inappropriate cyto-kine pattern, i.e. missing interferon or missing tumor necrosis factor, the same response may dramatically enhance tumor growth.