MGL Ligand Expression Is Correlated to Lower Survival and Distant Metastasis in Cervical Squamous Cell and Adenosquamous Carcinoma.

Cervical cancer is the fourth most common cancer type in women worldwide and is characterized by a highly immune-suppressive microenvironment. Here, we describe aberrant glycosylation as a factor mediating this immunosuppressive microenvironment. Expression of a specific carbohydrate ligand for the immune-regulatory C-type lectin MGL was correlated to poor disease-specific survival and distant recurrences in squamous cell carcinoma (SCC) and adenosquamous carcinoma (ASC), the most common histological subtypes of cervical cancer. MGL ligand expression was also associated with lymph node metastasis, the absence of CD14(+) myeloid cells and the presence of CD14(-)CD163(+) myeloid cells. Indeed, expression of the MGL receptor itself could be detected on CD163(+) cells, suggesting that MGL(+) myeloid cells are able to interact locally with MGL ligand(+) tumor cells. Additionally, MGL ligand expression correlated to the occurrence of PIK3CA mutations, the most frequently observed oncogenic alteration in cervical cancer. In conclusion, we present prognostic value for MGL ligand expression in SCC/ASC patients, which further supports an immune evasive role for the C-type lectin MGL in the tumor immune compartment.