Innate immunity, inflammation and cancer

The presence of an inflammatory microenvironment can favour tumor formation, thus immunotherapy can be a valid approach for the treatment of tumor. PTX3 gene is involved in microbial recognition, opsonization, complement activation and regulation of leukocyte recruitment and inflammation. The contribution of PTX3 to cancer development has been investigated by using a mouse model that develops cancer spontaneously. PTX3 knock-out mice show a higher incidence of sarcoma and papilloma. In addition, tumors in PTX3 knock-out mice produce a higher amount of pro-inflammatory cytokines and chemokines. Finally, PTX3-deficiency is associated with increased p53 mutations in cancer cell lines and higher DNA-damage response, arguing for a protective role of PTX3 in preventing genetic instability. Furthermore, in several human tumors, PTX3 promoter is highly methylated, supporting the idea that the silencing of PTX3 favours tumor progression.