A*STAR scientists discover immune defect causing inherited self-healing skin cancer


Findings point to novel ways to treat chronic skin diseases and refractory skin cancer


Scientists from A*STAR’s Institute of Medical Biology (IMB) and Institute of Molecular and Cell Biology (IMCB) have discovered a novel immune defect that causes inherited recurrent skin cancer and skin inflammation. This discovery represents a significant breakthrough in the study of cancer immunology, and presents a new strategy to treat chronic skin diseases and skin cancer.

The team led by Prof. Bruno Reversade, together with international collaborators carried out experiments to identify the genetic mutations that are responsible for the recently-described skin cancer syndrome known as Multiple Self-healing Palmoplantar Carcinoma (MSPC).

They found that MSPC is caused by mutations in NLRP1, an ‘orphan’ immune-related gene that had not been previously known by the scientific community to cause human diseases.  NLRP1 mutations were found to cause the misfiring of the immune system specifically within the patients’ skin, making them highly prone to developing skin cancer.

This discovery identifies NLRP1 as an attractive drug target to treat chronic skin inflammatory conditions such as eczema and psoriasis, as well as aggressive skin cancer that is refractory to surgery. These findings were published in the 23 September 2016 issue of the prestigious journal Cell.

Chronic inflammatory skin diseases and skin cancer represent large disease burdens worldwide and are often caused by unknown factors, reflecting a significant gap in the knowledge in their pathogenesis. The team’s findings further revealed that NLRP1 functions as part of a larger cellular complex known as the inflammasome, which plays an unexpected role as an integrator and mediator of skin inflammation. This is the first time that the inflammasome has been implicated in skin inflammatory diseases and skin cancer.

Dr. Reversade added, ‘This is a significant illustration of how studying rare diseases can benefit the research on common ailments afflicting the general population. Given that the NLRP1 gene is highly variable, we expect that it will be a major determinant of one’s general skin health.’

Professor Hong Wan Jin, Executive Director of IMCB said, “The findings of this study has significant impact on immunology, cancer biology and cancer immunotherapy. I am confident that the study will pave the way for future translational research for innovative therapeutic solutions in skin cancer.”

The work is led by co-first authors, Dr. Franklin Zhong and Dr. Ons Mamai under the tutelage of Dr Bruno Reversade in collaboration with a large team of international scientists and clinicians from Tunisia, Egypt, Romania, France, Japan and the UK.

For the original publication, please refer to the paper, “Germline NLRP1 Mutations Cause Skin Inflammatory and Cancer Susceptibility Syndromes via Inflammasome Activation” published in Cell on 23 September 2016.