PUBLICATIONS
OUR LAB
Targeting Cancer-Associated Glycosylation
for Adoptive T-Cell Therapy of Solid Tumors
[ Cancer Immunology Research, 2025 ]
Describes the development of a fully human CAR with a glyco-target: the truncated, sialylated O-glycan Sialyl-Thomsen-nouveau (STn) antigen, expressed in different solid tumors. Anti-STn CAR T cells showed activity in mouse models, as well as in assays with primary ovarian cancer samples.
Melanoma Clonal Heterogeneity Leads to Secondary Resistance after Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes
[ Cancer Immunology Research, 2024 ]
Reports the case of a melanoma patient who relapsed after responding to tumor-infiltrating lymphocyte (TIL) adoptive cell therapy (ACT) due to the outgrowth of a pre-existing, therapy-resistant tumor cell clone selected by the infused T cells. This finding highlights the need to assess tumor diversity (and sampling multiple lesions) to improve ACT.
Engagement of sialylated glycans with Siglec receptors on suppressive myeloid cells inhibits anticancer immunity via CCL2
[ Cellular & Molecular Immunology, 2024 ]
Reveals that hypersialylated myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment engage inhibitory Siglec receptors, enhancing expression of CCL2 and dampening anti-tumor T cell responses. Blocking Siglec signaling or enzymatically removing sialic acids diminishes MDSC suppression, promotes T cell tumor infiltration, and significantly improves survival in mouse cancer models.
Targeting cancer glycosylation repolarizes tumor-associated macrophages allowing effective immune checkpoint blockade
[ Science Translational Medicine, 2022 ]
Describes that hypersialylation is linked to suppressed immune activity and poorer survival in human cancers, and that targeted removal of these sialic acids via an antibody–sialidase conjugate enhances antitumor immunity and survival in vivo. Desialylation repolarizes tumor-associated macrophages through Siglec‑E inhibition and significantly boosts the efficacy of immune checkpoint blockade therapies.
Siglec Receptors Modulate Dendritic Cell Activation and Antigen Presentation to T Cells in Cancer
[ Frontiers in Cell and Developmental Biology, 2022 ]
Shows that classical dendritic cells (DCs) in human tumors highly express inhibitory Siglec receptors, e.g. Siglec‑7, Siglec‑9, and Siglec‑10, and that murine tumor‑associated cDCs upregulate Siglec‑E. Genetic deletion of these Siglecs restores DC maturation and enhances their ability to prime antigen‑specific CD4⁺ T cells, suggesting that targeting DC‑expressed Siglecs could potentiate cancer immunotherapy.
Hyperglycemia Enhances Cancer Immune Evasion by Inducing Alternative Macrophage Polarization through Increased O-GlcNAcylation
[ Cancer Immunology Research, 2020 ]
Reports that, in cancer, hyperglycemia increases flux through the hexosamine biosynthetic pathway, thereby upregulating protein O‑GlcNAcylation in tumor-associated macrophages. This shifts macrophages toward an immunosuppressive phenotype and promotes tumor growth in mice. This mechanism was also observed in human colorectal cancer patients with type 2 diabetes, underscoring the potential for targeting glycosylation or controlling blood glucose levels to reverse TAM-mediated immune evasion.
Self-associated molecular patterns mediate cancer immune evasion by engaging Siglecs on T cells
[ The Journal of Clinical Investigation, 2018 ]
Identified that human tumor-infiltrating T cells upregulate inhibitory CD33-related Siglecs—particularly Siglec‑9—which bind tumor-expressed sialylated glycans and dampen T cell receptor signaling, contributing to immune evasion. Therapeutically, blocking the sialic acid–Siglec axis restores T cell activation, boosting antitumor immunity and suggesting a novel glyco-immune checkpoint target analogous to PD‑1/CTLA‑4 blockade.
REVIEWS
COLLABORATIONS
Plückthun, Zurich, CH
CLINIC
