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Updated: Jan 19, 2026
Introduction to Innate and Adaptive Immunity
The sialoglycan-Siglec glyco-immune checkpoint - a target for improving innate and adaptive anti-cancer immunity
Anne Bärenwaldt1, Heinz Läubli1
1Division of Medical Oncology, and Laboratory for Cancer Immunotherapy, Department of Biomedicine, University Hospital Basel , Basel , Switzerland.
Abstract:
Introduction: During cancer progression, tumor cells develop several mechanisms to prevent killing and to shape the immune system into a tumor-promoting environment. One of such regulatory mechanism is the overexpression of sialic acid (Sia) on carbohydrates of proteins and lipids on tumor cells. Sia-containing glycans or sialoglycans were shown to inhibit immune effector functions of NK cells and T cells by engaging inhibitory Siglec receptors on the surface of these cells. They can also modulate the differentiation of myeloid cells into tumor-promoting M2 macrophages. Areas covered: We review the role of sialoglycans in cancer and introduce the Siglecs, their expression on different immune cells and their interaction with cancer-associated sialoglycans. The targeting of this sialoglycan-Siglec glyco-immune checkpoint is discussed along with potential therapeutic approaches. Pubmed was searched for publications on Siglecs, sialic acid, and cancer. Expert opinion: The targeting of sialoglycan-Siglec interactions has become a major focus in cancer research. New approaches have been developed that directly target sialic acids in tumor lesions. Targeted sialidases that cleave sialic acid specifically in the tumor, have already shown efficacy; efforts targeting the sialoglycan-Siglec pathway for improvement of CAR T cell therapy are ongoing. The sialoglycan-Siglec immune checkpoint is a promising new target for cancer immunotherapy.
Insights
Cancer cells use sialic acids (Sia) to evade immune attack by engaging Siglec receptors. Targeting this Sia-Siglec interaction offers a promising new avenue for cancer immunotherapy.
Area of Science:
- Immunology
- Glycobiology
- Cancer Biology
Background:
- Tumor cells evade immune surveillance through mechanisms like sialic acid (Sia) overexpression.
- Sialic acid-containing glycans (sialoglycans) on tumor cells inhibit immune cells (NK, T cells) and promote M2 macrophage differentiation.
- Siglec receptors on immune cells bind to cancer-associated sialoglycans, contributing to immune suppression.
Purpose of the Study:
- To review the role of sialoglycans in cancer progression.
- To introduce Siglecs and their interactions with cancer-associated sialoglycans.
- To discuss targeting the sialoglycan-Siglec glyco-immune checkpoint for therapeutic strategies.
Main Methods:
- Literature review of publications on Siglecs, sialic acid, and cancer using PubMed.
- Analysis of the interaction between sialoglycans and Siglec receptors in the tumor microenvironment.
- Exploration of therapeutic approaches targeting the sialoglycan-Siglec pathway.
Main Results:
- Sialoglycan-Siglec interactions represent a significant mechanism of immune evasion in cancer.
- Targeting sialic acids directly, for example, with sialidases, shows efficacy in tumor lesions.
- Ongoing research aims to leverage the sialoglycan-Siglec pathway to enhance CAR T cell therapy.
Conclusions:
- The sialoglycan-Siglec axis is a critical glyco-immune checkpoint in cancer.
- Targeting this pathway presents a promising strategy for novel cancer immunotherapies.
- Developing therapies that disrupt sialoglycan-Siglec interactions can restore anti-tumor immunity.
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