Artículo
The Tn antigen promotes lung tumor growth by fostering immunosuppression and angiogenesis via interaction with Macrophage Galactose-type lectin 2 (MGL2)
da Costa, Valeria; van Vliet, Sandra J.; Carasi, Paula
; Frigerio, Sofía; García, Pablo A.; Croci Russo, Diego Omar
; Festari, María Florencia; Costa, Monique; Landeira, Mercedes; Rodríguez Zraquia, Santiago A.; Cagnoni, Alejandro
; Cutine, Anabela María
; Rabinovich, Gabriel Adrián
; Osinaga, Eduardo; Mariño, Karina Valeria
; Freire Gard, Teresa Inés
Fecha de publicación:
10/10/2021
Editorial:
Elsevier Ireland
Revista:
Cancer Letters
ISSN:
0304-3835
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Tn is a tumor-associated carbohydrate antigen that constitutes both a diagnostic tool and an immunotherapeutic target. It originates from interruption of the mucin O-glycosylation pathway through defects involving, at least in part, alterations in core-1 synthase activity, which is highly dependent on Cosmc, a folding chaperone. Tn antigen is recognized by the Macrophage Galactose-type Lectin (MGL), a C-type lectin receptor present on dendritic cells and macrophages. Specific interactions between Tn and MGL shape anti-tumoral immune responses by regulating several innate and adaptive immune cell programs. In this work, we generated and characterized a variant of the lung cancer murine cell line LL/2 that expresses Tn by mutation of the Cosmc chaperone gene (Tn+ LL/2). We confirmed Tn expression by lectin glycophenotyping and specific anti-Tn antibodies, verified abrogation of T-synthase activity in these cells, and confirmed its recognition by the murine MGL2 receptor. Interestingly, Tn+ LL/2 cells were more aggressive in vivo, resulting in larger and highly vascularized tumors than those generated from wild type Tn− LL/2 cells. In addition, Tn+ tumors exhibited an increase in CD11c+ F4/80+ cells with high expression of MGL2, together with an augmented expression of IL-10 in infiltrating CD4+ and CD8+ T cells. Importantly, this immunosuppressive microenvironment was dependent on the presence of MGL2+ cells, since depletion of these cells abrogated tumor growth, vascularization and recruitment of IL-10+ T cells. Altogether, our results suggest that expression of Tn in tumor cells and its interaction with MGL2-expressing CD11c+F4/80+ cells promote immunosuppression and angiogenesis, thus favoring tumor progression.
Palabras clave:
ANGIOGENESIS
,
LUNG CANCER
,
MACROPHAGE GALACTOSE-TYPE LECTIN
,
TN ANTIGEN
,
TREG
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Articulos(IBYME)
Articulos de INST.DE BIOLOGIA Y MEDICINA EXPERIMENTAL (I)
Articulos de INST.DE BIOLOGIA Y MEDICINA EXPERIMENTAL (I)
Articulos(IIFP)
Articulos de INST. DE ESTUDIOS INMUNOLOGICOS Y FISIOPATOLOGICOS
Articulos de INST. DE ESTUDIOS INMUNOLOGICOS Y FISIOPATOLOGICOS
Citación
da Costa, Valeria; van Vliet, Sandra J.; Carasi, Paula; Frigerio, Sofía; García, Pablo A.; et al.; The Tn antigen promotes lung tumor growth by fostering immunosuppression and angiogenesis via interaction with Macrophage Galactose-type lectin 2 (MGL2); Elsevier Ireland; Cancer Letters; 518; 10-10-2021; 72-81
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