New! Sign up for our free email newsletter.
Science News
from research organizations

Cancer's sweet Achilles heel

Unlocking the power of sugar chains holds a key to cancer immunotherapy

Date:
October 25, 2023
Source:
Kyoto University
Summary:
A high expression of the enzyme beta1,4-galactosyltransferase-3, or B4GALT3 is associated with noticeably shortened survival rates in several types of immunotherapy cancersdeficiency in mice TIME inhibits tumor growth. The study shows that a significant reduction of glycosylation -- a type of protein modification -- on T cell surfaces correlates with increases in CD8+ immune cells infiltrating tumors. Weakly immunogenic and strongly immunogenic tumor cells were subcutaneously transplanted  into B4GALT3 knockout and wild-type mice, to examine for tumor cell growth. Only the knockout mice suppressed the growth of strongly immunogenic tumor cells.
Share:
FULL STORY

An old campaign slogan for cough syrup, "It tastes awful. And it works," seemed to imply that any sweet content might have diminished the medicinal effect.

Sweetness, in the case of cancer, appears as a chain of sugar molecules attached to proteins by beta1,4-galactosyltransferase-3, or B4GALT3 According to the Cancer Genome Atlas, a high expression of this enzyme is associated with noticeably shortened survival rates in several types of immunotherapy cancers, such as neuroblastoma, cervical, and bladder cancer. However, the specific role of B4GALT3 in the tumor immune microenvironment -- or TIME -- was still unknown.

Now, a team of researchers at Kyoto University and Yokohama City University has found that B4GALT3 deficiency in mice TIME inhibits tumor growth. The study shows that a significant reduction of glycosylation -- a type of protein modification -- on T cell surfaces correlates with increases in CD8+ immune cells infiltrating tumors.

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

By purifying membrane proteins and enzymatically cleaving them to enrich glycopeptides, the team could identify the sites and structures of glycans -- complex and highly branched sugar chains -- and the amount of glycoproteins. The role of glycans has attracted much attention in studies on cancer cells, which proliferate and metastasize, depending on their interaction with their microenvironment.

The team subcutaneously transplanted weakly immunogenic and strongly immunogenic tumor cells into B4GALT3 knockout and wild-type mice, to examine for tumor cell growth. Only the knockout mice suppressed the growth of strongly immunogenic tumor cells.

In addition, the increased CD8+ T cells in knockout mice secreted anti-cancer compounds Interferon-γ and Granzyme B.

"We found that the loss of B4GALT3 caused significant fluctuations in gene expression in the immune system, a discovery which has significantly changed the direction of our next phase of research," adds coauthor Chie Naruse.

"We have gained insight into the role of glycans in cancer progression and immune response, inspiring possibilities of B4GALT3-centered cancer therapies," says team leader Masahide Asano.


Story Source:

Materials provided by Kyoto University. Note: Content may be edited for style and length.


Journal Reference:

  1. Heng Wei, Chie Naruse, Daisuke Takakura, Kazushi Sugihara, Xuchi Pan, Aki Ikeda, Nana Kawasaki, Masahide Asano. Beta-1,4-galactosyltransferase-3 deficiency suppresses the growth of immunogenic tumors in mice. Frontiers in Immunology, 2023; 14 DOI: 10.3389/fimmu.2023.1272537

Cite This Page:

Kyoto University. "Cancer's sweet Achilles heel." ScienceDaily. ScienceDaily, 25 October 2023. <www.sciencedaily.com/releases/2023/10/231025223428.htm>.
Kyoto University. (2023, October 25). Cancer's sweet Achilles heel. ScienceDaily. Retrieved June 21, 2024 from www.sciencedaily.com/releases/2023/10/231025223428.htm
Kyoto University. "Cancer's sweet Achilles heel." ScienceDaily. www.sciencedaily.com/releases/2023/10/231025223428.htm (accessed June 21, 2024).

Explore More

from ScienceDaily

RELATED STORIES