Tn TUMOR ASSOCIATED CARBOHYDRATE ANTIGEN PROMOTES THE GROWTH OF VASCULARIZED TUMORS

DA COSTA ESCARÓN, VALERIA; FREIRE, TERESA; MARIÑO, KARINA VALERIA; OSINAGA, EDUARDO

Ciudad de México

Congreso; Quinto Congreso Latinoamericano de Glicobiología; 2019

Sociedad Latinoamericana de Glicobiología

The Tn antigen (GalNAc-O-Ser/Thr) is a tumor-associated carbohydrate antigen expressed in 90% of adenocarcinomas. It constitutes both a diagnostic tool and a target for immunotherapies. Tn originates from a blockage in the O-glycosylation pathway, which prevents Tn to be elongated to core 1, by the core-1-synthase and its associated chaperone, COSMC. Previous studies show that the presence of Tn is associated with malignancy and is related to the metastasis potential of the tumor cell. Furthermore, this antigen is recognized by the C-type receptor MGL, present on dendritic cells and macrophages, and it may modulate the immune response towards the tumor. In this study, we developed a tumoral model to study the immunomodulatory role of Tn during tumor growth. Particularly, we generated variants of the lung cancer murine cell line, LL2 (Tn negative) expressing different levels of Tn by mutations in the COSMC chaperone gene. We confirmed the expression of Tn with specific lectins, such as VVL and HPA, using an antibody against Tn, evaluated the T-synthase activity and confirmed recognition by the MGL2 murine receptor. Interestingly, when inoculated in syngeneic mice, Tn+ cells produced tumors that grew faster and presented higher levels of vascularization. In addition, Tn+ cell tumors presented more CD11c+ F4/80+ cells that expressed higher level of MGL2, together with an increased expression of FoxP3 and regulatory cytokines, such as IL10 and IL4, in infiltrating CD4+ T cells. These results indicate that Tn has a relevant role in the tumor development, and suggest that it may be responsible for immunomodulatory processes triggered by the tumor cells.