# GlycoChat Uncovers Glycan–Lectin Circuits in the Tumor Microenvironment of Pancreatic Cancer

## TL;DR

This study introduces GlycoChat, a new tool that reveals how cancer cells use sugar molecules to manipulate immune cells in pancreatic cancer, offering new therapeutic targets.

## Contribution

The development of GlycoChat, a novel analytical framework for mapping glycan–lectin circuits at single-cell resolution in the tumor microenvironment.

## Key findings

- GlycoChat identified CLEC10A and SIGLEC3 as lectin receptors on tumor-associated macrophages interacting with cancer cell glycans.
- Cancer cells promote immunosuppressive macrophage differentiation and impair phagocytic activity via these interactions.
- The study highlights glyco-immune checkpoints as potential therapeutic targets in pancreatic cancer.

## Abstract

Aberrant glycosylation is a hallmark of cancer progression, yet its functional implications within the tumor microenvironment (TME) remain poorly understood. Here, a single‐cell glycomic profiling strategy was applied to tumor tissues from patients with pancreatic ductal adenocarcinoma (PDAC), enabling the identification of cell‐type‐specific glycome signatures and their dynamic alterations during the transition from classical to basal‐like cancer subtypes. To systematically decode glycan‐mediated communication in the TME, an analytical framework termed GlycoChat was developed for mapping global glycan–lectin circuits at single‐cell resolution. GlycoChat identified CLEC10A and SIGLEC3 as lectin receptors expressed on tumor‐associated macrophages that interact with cancer cell surface glycans. Functional assays demonstrated that cancer cells promote differentiation of immunosuppressive macrophages and impair phagocytic activity through interactions with CLEC10A and SIGLEC3. This study establishes GlycoChat as a powerful tool for dissecting glycan–lectin circuits in complex TME and highlights glyco‐immune checkpoints as potential targets for therapeutic intervention in PDAC.

Aberrant glycosylation drives cancer progression, yet its role in the tumor microenvironment remains unclear. We developed GlycoChat to map glycan–lectin circuits at single‐cell resolution. We discovered that cancer cells induce immunosuppressive macrophage differentiation and impair phagocytosis through interactions with CLEC10A and SIGLEC3, highlighting novel glyco‐immune checkpoints as promising therapeutic targets.