Tumor-associated truncated core 1 O-glycan-expressing granulocytic myeloid-derived suppressor cell and neutrophil (Tn-G-MDSC/Neutrophil)

Granulocytic myeloid-derived suppressor cells (G-MDSCs) and neutrophils expressing tumor-associated truncated core 1 O-glycans represent a specialized subset of immunosuppressive cells within the tumor microenvironment. These cells are characterized by the presence of immature O-glycans, such as the Tn antigen (GalNAc-alpha-Ser/Thr) and Sialyl-Tn (STn), which arise due to dysfunctional glycosylation machinery, such as the loss of the molecular chaperone Cosmc, common in malignant transformation (Beatson et al., 2020). While healthy neutrophils typically express complex, elongated O-glycans, the G-MDSCs in many solid tumors display these immature glycoforms on surface proteins like MUC1 and CD43, making them distinct from their healthy counterparts (Posey et al., 2016). This unique glycosylation pattern serves as a selective target for therapeutic intervention, particularly for chimeric antigen receptor (CAR) T-cell therapies and monoclonal antibodies. Targeting these cells allows for the specific depletion of the myeloid-derived suppressive shield, thereby enhancing the anti-tumor activity of endogenous T-cells and reversing the immunosuppressive state of the tumor microenvironment (Cornelissen et al., 2020). Such strategies aim to improve the efficacy of existing immunotherapies by removing the barriers posed by these specialized myeloid populations (Gabrilovich, 2017).

Other names

Tn-positive granulocytic myeloid-derived suppressor cellSialyl-Tn-positive neutrophilTruncated O-glycan-expressing myeloid cellTn-MUC1-expressing G-MDSCTn-CD43-expressing neutrophil

Selective elimination of immunosuppressive myeloid cells via chimeric antigen receptor (CAR) T-cell recognition or antibody-dependent cellular cytotoxicity (ADCC), leading to the relief of T-cell suppression and enhancement of anti-tumor immunity.