α2,6-Sialoglycan-regulated antitumor immunity of tumor-infiltrating CD8(+) T cells.

Downregulation of α2,6-sialoglycans marks high-avidity intratumoral tumor-specific antigen-reactive CD8+ T cells in murine tumors, linking linkage-specific sialylation to T-cell state.

• Why it matters: Cell-surface sialoglycans suppress activation of tumor-infiltrating immune cells, but how α2,3- versus α2,6-sialylation functionally relates to TIIC gene programs is unclear.
• What they did: The study used single-cell RNA sequencing with a strategy for correlative, linkage-specific profiling of α2,3- and α2,6-linked sialoglycans and matched transcriptomes across TIIC subpopulations in murine tumors.
• The result: High-avidity CD8+ T-cell activation suppressed β-galactoside α2,6-sialyltransferase 1, exposing galectin-1 ligands; galectin-1 binding promoted T-cell apoptosis and immune evasion, suggesting therapeutic targeting of specific sialoglycans.

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