Complement enhances tumour evasion


A seemingly illogical link between activation of immune sensors and the ability of tumours to escape the immune system. The unexpected result reveals a new drug target for cancer treatment.

The complement system comprises a cascade of proteins that act as a fire alarm to alert the immune system to the presence of infection. In a bizarre twist, Lambris and colleagues show that tumour activation of one of the complement proteins – C5 – in fact leads to suppression of the anti-tumour immune response.

The surprising outcome is explained by the observation that the activated protein recruits ‘suppressor’ cells to the site. These act to disarm other immune cells and stop them from killing the tumour. Importantly, the authors show that blocking the activity of C5 slows tumour growth in mice and this treatment is as effective as taxol, a commonly used anti-cancer drug.

Author contact:
John Lambris (University of Pennsylvania, Philadelphia, PA, USA)
Tel: +1 215 746 5765; E-mail: lambris@mail.med.upenn.edu

Fountain of youth



Researchers have identified the cells that provide an essential survival factor to newly created immune cells.

White blood cells known as T lymphocytes are born in the thymus and these cells are required to fight off viral and other infections. Upon leaving the thymus these cells prowl throughout the body seeking out potential foreign agents; however, the survival of these cells depends on periodic visits to lymph nodes, where they can ‘recharge’ by receiving a chemical signal called interleukin 7 (IL-7).

It was known for many years that IL-7 provides ‘survival’ signals to these naive T cells, but what actually produced IL-7 proved elusive. Sanjiv Luther and colleagues identify specialized ‘fibroblastic reticular cells’ found in lymph nodes and spleen as the source of IL-7. These cells make chemical signals that direct T cells to them and supply the essential IL-7 that prevents T cells from dying, thereby allowing them to continue to recirculate throughout the body searching for enemies.



Author contact:

Sanjiv Luther (University of Lausanne, Epalinges, Switzerland)

Tel: +41 21 692 5678; E-mail: sanjiv.luther@unil.ch

Dialling up damage responders


Certain cells of the immune system more readily tolerate damage to their genes than other cells, up to a point. New research shows the protein BCL6, expressed in antibody-producing B cells, senses how much DNA damage is occurring inside these cells and activates repair pathways when damage becomes excessive.

BCL6 is a repressor that blocks expression of DNA repair enzymes in the presence of small amounts of damage. This suppression is beneficial to the B cells as these cells can ‘fine-tune’ their antibody responses by mutating the antibody genes or undergoing what is called ‘class switch recombination’, a genetic rearrangement that allows different types of antibodies to be produced.

Riccardo Dalla-Favera and colleagues show excessive DNA damage in these B cells can be recognized by BCL6. BCL6 acts as a ‘damage-sensitive’ resistor that, once tipped beyond a threshold amount of accumulated DNA breaks, initiates a pathway that leads to its own destruction and turns on repair enzymes. These findings further our understanding of BCL6, which is commonly found to be mutated in forms of B cell cancers, and may thereby be instructive in designing therapies to blunt BCL6 activity in these cancers.


Author contact:

Riccardo Dalla-Favera (Columbia University, New York, NY, USA)

Tel: +1 212 851 5273; E-mail: rd10@columbia.edu



Stem cells have nervous impulses


Blood stem cells become activated in response to signals released by nerve cells according to a research.

Tsvee Lapidot and colleagues report bone marrow stem cells express dopamine receptors. Release of neurotransmitters, as occurs during times of stress, triggers the blood cells to divide and migrate from their protected bone marrow environment. Treatment of mice with dopamine or other neurotransmitters led to increased numbers of these stem cells in bone marrow and in the blood circulation. Neurotransmitter stimulation of human bone marrow cells likewise increased their engraftment potential upon transplantation into ‘humanized mouse’ recipients, whose immune system is reconstituted by the human cells. Such findings might translate to increased efficiency of therapies that require bone marrow transplantation.

Author contact:

Tsvee Lapidot (Weizmann Institute of Science, Rehovot, Israel)

Tel: +972 8 934 2481; E-mail: Tsvee.Lapidot@weizmann.ac.il