A sugar-enzyme link to tumour growth suppression


A chain of sugar molecules attached to proteins may hold the key to fighting cancer. These sugar-protein chains, regulated by an enzyme called beta1,4-galactosyltransferase-3 (B4GALT3), have surfaced as crucial players in various cancers, particularly impacting survival rates in immunotherapy-sensitive cancers like neuroblastoma, cervical, and bladder cancer. Yet, the specific role of B4GALT3 within the tumour immune microenvironment (TIME) remained enigmatic.

In a recent study, researchers have unravelled the mystery behind B4GALT3’s role within the TIME. They discovered that a deficiency of B4GALT3 in mice’s TIME leads to the inhibition of tumour growth. This study underscores the significance of glycosylation, a form of protein modification, on the surfaces of T cells. It has revealed that when glycosylation is significantly reduced, it paves the way for increased infiltration of CD8+ immune cells into tumours. In the case of B4GALT3 knockout (KO) mice, these findings offer a new avenue for manipulating T cell surface glycosylation, presenting a promising approach to cancer immunotherapy.

To understand the sugar-protein connection, the research team used a method involving the purification of membrane proteins and enzymatic cleavage to enrich glycopeptides. This allowed them to identify the sites and structures of glycans – complex, highly branched sugar chains – and quantify glycoproteins.

The study’s experimental approach involved the subcutaneous transplantation of tumour cells, both weakly and strongly immunogenic, into B4GALT3 knockout and wild-type mice to investigate tumour growth. Only the knockout mice exhibited suppressed growth of highly immunogenic tumour cells. Furthermore, the knockout mice showed elevated levels of CD8+ T cells, which secreted potent anti-cancer compounds, including Interferon-γ and Granzyme B.

These remarkable findings open new possibilities for cancer immunotherapy, emphasizing the pivotal role of B4GALT3 in the battle against cancer. It suggests that manipulating glycosylation of T cell surfaces could be the key to enhancing the immune response against tumors and holds promise for the future of cancer treatment.

Journal article: Wei, H., et al., 2023. Beta-1,4-galactosyltransferase-3 deficiency suppresses the growth of immunogenic tumors in mice. Frontiers in Immunology.

Summary by Stefan Botha

International Union of Immunological SocietiesUniversity of South AfricaInstitute of Infectious Disease and Molecular MedicineElizabeth Glazer Pediatric Aids Foundation