Sugar chains as key to advanced immunotherapy

B4GALT3 deficiency in mice reduces tumor growth and alters immune responses, suggesting new cancer treatment strategies.

An old campaign slogan for cough medicine was, “It tastes terrible. It works,” indicating that any sweetener content may have reduced the clinical effect.

Role of B4GALT3 in cancer progression

Sweetness, in the case of cancer, appears to be a chain of sugar molecules attached to proteins. Beta1,4-galactosyltransferase-3Or B4GALT3. According to the Cancer Genome Atlas, high expression of this enzyme is associated with significantly shortened survival rates in several types of immunotherapy cancers, such as neuroblastoma, cervical and bladder cancer. However, the specific role of B4GALT3 The tumor immune microenvironment – Or Time – Not sure yet.

Weakly immunogenic and strongly immunogenic tumor cells were transplanted subcutaneously into B4GALT3 knockout and wild-type mice. Tumor cell growth was significantly suppressed in knockout mice. Credit: KyotoU Jake Tobiyama/Heng Wei

Breakthrough study of B4GALT3 and cancer

Now, a team of researchers from Kyoto University and Yokohama City University has found that B4GALT3 deficiency in mice inhibits tumor growth. The study showed a significant reduction Glycosylation – a type of protein change – associated with an increase in T cell surfaces CD8+ immune cells Invasive tumors.

„In B4GALT3 knockout or KO mice, we demonstrated the ability to manipulate T cell surface glycosylation as a new approach for cancer immunotherapy,” says Heng Wei of Kyoto University's Graduate School of Medicine.

Understanding glycans in cancer cells

by purifying membrane proteins and enzymatically cleaving them to enrich them GlycopeptidesBe able to identify group sites and structures Glycans – complex and highly branched sugar chains – and size Glycoproteins. The role of glycans has attracted much attention in studies on cancer cells, which proliferate and adapt depending on interactions with their microenvironment.

Experimental findings and future directions

The group was transplanted subcutaneously Weak immunity And Strong immunity Tumor cells from B4GALT3 knockout and wild-type mice to examine tumor cell growth. Only the knockout mice suppressed the growth of strongly immune tumor cells.

In addition, the knockout mice had increased CD8+ T cells secreting anticancer compounds Interferon-γ And Granzyme B.

„We found that the loss of B4GALT3 caused significant fluctuations in gene expression in the immune system, which significantly changed the direction of our next phase of research,” says co-author Sea Naruse.

„We have gained insight into the role of glycans in cancer progression and immune response, promoting the potential of B4GALT3-targeted cancer therapy,” says team leader Masahide Asano.

Reference: „beta-1,4-galactosyltransferase-3 deficiency suppresses growth of immunogenic tumors in mice” , Frontiers in Immunology.
DOI: 10.3389/fimmu.2023.1272537