Women who have a deficient immune response, such as AIDS patients, develop uterine cervical cancer more often. This suggests that the immune system plays an important role in the fight against this particular cancer. However, the cells involved in this immune response are not well defined. “In the literature, an infiltration of the NK cells has been described in the lesions associated with HPV infection while these cells are very rare in the normal tissues corresponding to these lesions. We have confirmed this infiltration of the NK cells with a more specific marker for these cells and therefore we have studied the interaction between this virus and these lymphocytes.”

In order to study the interaction with the virus, it was not possible to use the virus directly because it is very difficult to produce the virus in a laboratory since it requires 3-D cell cultures to grow.“We therefore carried out our experiments using virus-like particles (VLP).,These pseudo particles look like a virus but they do not contain its genetic material. These same VLPs are present in the existing vaccines against uterine cervical cancer.”

Thanks to these virus pseudo particles, the ULg team  showed that the NK cell was capable of recognizing the virus and internalizing it via a receptor present on their surface, the CD16.  Interestingly, when the NK cells interact with the virus, they produce cytokines (i.e. interferon-γ) which can amplify the immune response. As the NK cells are killer cells, their lysing activity has also been analysed. The virus pseudo particles induce the release of perforins and granzymes contained in the cytotoxic granules of NK cells. HPV+ cancer cells which express molecules recognized by NK cell activating receptors are then lysed more efficiently by NK cells. On the other hand, the normal epithelial cells which do not express molecules that can be recognized by the NK cells are not sensitive to their cytotoxic activity in the presence of VLPs. “These results strongly suggest that the NK cells have a role in the host response against HPV infection. However, we are the first to have shown the activity of these cells in this pathology and not everyone is ready to believe us yet. It is up to us to convince them by improving our knowledge about NK cell mechanisms of action”.

This pioneering research on the role of NK cells against uterine cervical cancer development could lead to more efficient ways of preventing disease. In any event, these cells have not yet revealed all their secrets and hold more big surprises in store.