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Pancreatic tumor rejection induced by autoimmune response


Immune responses are capable of killing tumors before they can be directed toward normal body tissue.

The findings are published in Cancer Research.

There are extremely precise mechanistic methods augmenting the ability of the immune system to distinguish between normal tissues and tumors. Understanding the multiple checks and safeguards against autoimmunity should allow to understand more closely how to generate antitumor immunity.

Vile, at the Mayo Clinic, Rochester, along with other colleagues, induced pathological damage to a normal organ, in this case the pancreas, with the immune adjuvant hsp70.
Researchers investigated whether that damage could lead to the development of T-cell responses against the normal pancreas.

Inflammatory killing of the normal pancreas induced a Th-1-like, anti-self response to pancreatic antigens. Rapid suppression and damage to the pancreas induced a very strong suppressive regulatory T-cell response, Treg. Even after Treg cells were depleted, Vile and colleagues found that Th-1-like response was insufficient to induce significant ongoing autoimmunity.

Based on this study, the researchers suggested that it is more difficult than presumed to induce autoimmunity against the pancreas because multiple immune safeguards exist to prevent potentially autoimmune T-cells from destroying the normal pancreas. Further, when comparing the immunoprotective mechanisms of different tissues, profound differences exist in response to pathogen-like damage.

Cancer Research editorial board member Ivan Borrello, at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, believes this study highlights several unique aspects of tumor immunology. The immune response toward normal elements and tumors in different organs are mediated through different mechanisms and may require different approaches to achieve a beneficial therapeutic outcome, he said. Further, in certain situations like the pancreas, it may not be sufficient to prime effective antitumor immunity.
This study demonstrates the increasing complexity within which both normal tissues and tumors can protect themselves against destruction and underscores the complex network regulating immune responsiveness.

These findings may lead to a new approach for the development of a cancer vaccination.

Source: American Association for Cancer Research, 2009

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