Investigating natural killers

Francesco Colucci

Dr Francesco Colucci researches a type of white blood cell called a Natural Killer (NK) cell, which destroys tumour and virally-infected cells. In doing so, he follows both a family and a King's tradition in medicine and immunology.

"I was always interested in nature and human evolution," he says, "and I had a role model in the family. My parents are not highly educated, but I had an uncle who, like me, came from southern Italy, got to medical school, then travelled and became interested in genetics and immunology. He inspired me to study medicine."

After medical school Francesco drifted away from clinical practice, and like his uncle travelled to Sweden, France and the UK and became interested in immunology.

It was during his post-doctoral training in Paris (1997-2000) that he started researching NK cells. He is now looking at how these cells can help treat cancer and prevent complications in pregnancy.

"This is an exciting time for immunologists with an interest in research and clinical practice in cancer because new anti-cancer drugs are being developed that may synergise with the body’s immune cells to fight cancer."

To understand how NK cells can be more effective in attacking cancer, Francesco is working with oncologists at Addenbrooke's Hospital and geneticists at the Wellcome Trust Sanger Institute. They are taking cells from patients before and after cancer treatment, and looking at what changes have occurred both within the cancer cells and in the molecular conversation between the NK cells and cancer cells.

"Cancer cells too often build resistance to the drugs, and we are trying to understand how to fight the mutant cancer cells by using new drugs and by harnessing the power of NK cells. If properly stimulated, the NK cells might help overcome the resistance of cancer cells to the drugs."

Drugs are a much cheaper option than immunotherapy, so if resistance to them can be understood and overcome, then cancer treatment will be hugely more effective.

Francesco's interest in NK cells has also taken him into another area: pregnancy and childbirth. Here he is following a King's tradition. He is the third generation of King's Fellows to work on immunology in the womb, the first being Professor Charlie Loke and the second being Professor Ashley Moffett, with whom Francesco collaborates.

The unborn baby is genetically only half matched to its mother, so a long-standing question is: why doesn't the immune system attack the foetus as a foreign body?

"We have now a modern outlook on how the mother's NK cells engage in a constructive communication with the placenta."

"During pregnancy", Francesco says, "NK cells become very numerous in the womb but they are no longer killers. In fact, they change their role completely and actually help the growth of the foetus. We don't understand how this happens, but the clue may lie in how NK cells interact with the placenta, an organ that is made and run by the foetus rather than the mother.

"In the future our knowledge of how NK cells interact with the placenta may lead to a treatment for pregnancy complications."

- February 2014

Dr Francesco Colucci is a University Reader at the University of Cambridge Clinical School. You can find a list of his key publications at the Department of Obstetrics and Gynaecology website, and watch talks about the immune system and the foetus on the University of Cambridge website. See also the news story about Francesco' research.

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