May 11, 2006

C-myc Required by the Immune System

Infamous proto-oncogene turns up in a new role

(May 11, Lausanne) – c-myc, a gene commonly involved in cancer onset, has been found to have a role in the immune system’s normal function according to a study published today in Blood. The surprising finding, by a Swiss research team led by investigators from the Lausanne Branch of the international Ludwig Institute for Cancer Research (LICR), showed that c-myc functions in the immune system’s ‘memory’ of previous infections.

In order to rapidly and efficiently respond to new infections, the immune system evolved such that it stores a ‘memory’ of previous attack by pathogens. The specialized cells involved in this process are known as ‘T memory cells’. The T memory cells are normally maintained at a low level that can be rapidly expanded if the pathogen is detected again. The maintenance of normal, low levels, or ‘homeostasis’, of T memory cells is dependent on a signalling factor, a so-called cytokine, known as ‘IL- 15.

“Very little is known about the signalling pathways that actually control IL-15-dependent homeostasis,” explains LICR’s Dr. H. Robson MacDonald, the senior author of the study. “By analyzing genetically engineered mouse models with reduced c-myc, reduced IL-15 or absent IL-15, we discovered that it’s actually c-myc, which is known primarily as an oncogene, that acts downstream of the IL-15 signaling pathway to regulate T memory cell homeostasis.”

According to Dr. MacDonald, the study is basic research that may have implications for therapies of the future. “Understanding how immune memory works might allow us to improve therapeutic vaccines against, say, malaria or cancer. The unexpected finding is that this study is also a cautionary tale. Before we design new therapies that inactivate a gene product, which is an approach being considered for c-myc in cancer, we need to be very sure that we are not going to be also destroying a vital role in a normal process such as the body’s immune system.”

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This study was conducted by investigators from the Lausanne Branch of the Ludwig Institute for Cancer Research (LICR), the Swiss Institute for Experimental Cancer Research (ISREC), and the Genetics and Stem Cell Laboratory of ISREC and Swiss Institute of Technology, all of which are situated in Lausanne, Switzerland.

For further details, please contact:

Dr. H. Robson MacDonald, Ludwig Institute for Cancer Research – Lausanne
+41 (0)21 692 59 89 (Business Hours, Lausanne; GMT +1 hour)
HughRobson.MacDonald@isrec.ch

Dr. Sarah L. White, Ludwig Institute for Cancer Research - New York
+1 212 450 1543 (Business Hours) / +1 917 974 7952 (After Hours, New York; GMT + 5 hours)
swhite@licr.org

The Ludwig Institute for Cancer Research (LICR) is the largest international academic institute dedicated to understanding and controlling cancer. With nine Branches in seven countries, and numerous Affiliates and Clinical Trial Centers in many others, the scientific network that is LICR quite literally covers the globe. The uniqueness of LICR lies not only in its size and scale, but also in its philosophy and ability to drive its results from the laboratory into the clinic. LICR has developed an


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