Transglutaminase type-2 (TG2) role in immune response against Skin Cutaneous Melanoma (SKCM).

Skin cutaneous melanoma (SKCM) is one of the most aggressive forms of cancers which arises from a series of inherited or acquired mutations in critical genes. The genetic background, in addition to UV rays induced DNA signatures, contribute to its development. Melanoma is reported to be highly immunogenic, mostly because of its mutational burden, that allows the production of several tumour specific antigens. However, its eradication isn’t often possible due to the activation of many immune escape mechanisms. In this context, we dissected the role of Transglutaminase type-2 (TG2) in immune system activation against melanoma. TG2 is an ubiquitously distributed multifunctional enzyme that modulates many cellular pathways implied both in immune activation or inhibition, thus favouring tumour promotion or its repression. This controversial behaviour likely depends on the tumour type, enzyme localization and conformational status, representing hypothetically both a positive or negative prognostic marker. We recently demonstrated by in silico studies that TG2 tends to guarantee a better overall survival in SKCM by enhancing immune-stimulating pathways. In this thesis, we evaluated the variations in the levels of pro-immunogenic cytokines and immune infiltrating cell populations in wild type and TG2 knock-out melanoma models confirming a TG2 positive role in melanoma prognosis.