Galectins: emerging regulatory checkpoints linking tumor immunity and angiogenesis

Area of Science:

• Immunology
• Cancer Biology
• Molecular Medicine

Background:

• Immune checkpoints are natural pathways that regulate immune responses and can be hijacked by tumors to escape immune surveillance.
• Current immunotherapies targeting immune checkpoints have shown significant success in treating various cancers by boosting anti-tumor immunity.
• Galectins, a family of glycan-binding proteins, are increasingly recognized for their role in immune regulation within the tumor microenvironment.

Purpose of the Study:

• To investigate the role of galectins as novel immune regulatory checkpoints in cancer.
• To explore how galectins promote tumor immune evasion through various cellular mechanisms.
• To evaluate the potential of targeting galectin-glycan interactions for cancer therapy.

Main Methods:

• Analysis of galectin functions in immune cell modulation, including T-cell exhaustion and regulatory T-cell expansion.
• Assessment of galectin's impact on natural killer cell activity and myeloid cell polarization.
• Investigation of galectin's role in vascular signaling and angiogenesis within tumors.

Main Results:

• Galectins induce T-cell exhaustion, limit T-cell survival, and promote regulatory T cells, contributing to immune evasion.
• Galectins deactivate natural killer cells and shift myeloid cells towards an immunosuppressive phenotype.
• Galectins act as bifunctional messengers, linking tumor immunity and angiogenesis through vascular signaling pathways.

Conclusions:

• Galectins function as critical checkpoints that facilitate tumor immune evasion.
• Targeting galectin-glycan interactions offers a dual therapeutic strategy.
• This approach may simultaneously enhance anti-tumor immunity and inhibit tumor angiogenesis, leading to halted tumor progression.