UW Carbone Cancer Center finds important protein for immunotherapies

Researchers at the UW Carbone Cancer Center have set their sights on a protein biomarker that could help doctors more accurately predict which patients are helped by certain treatments.

This biomarker is part of the tumor microenvironment, or matrix, which is made up of the non-cancerous cells and tissues surrounding a cancerous growth.

“To understand who might benefit from immunotherapies, we need to know what controls the immune microenvironment and what controls the infiltration of T cells, and this study is a big step in that direction,” said Dusty Deming, a physician-researcher specializing in colon cancer.

T cells are types of white blood cells that play a large role in immunity. Several distinct types of T cells exist, including ones that boost other white blood cells’ response to invaders, some that hunt down and kill virus-infected or tumor cells, and others that recognize these unwanted cells based on previous encounters.

Deming says cancers that are infiltrated by T cells usually have better outcomes in early stages, and also react more favorably to immunotherapies, which improve the immune system’s reaction to cancer.

He partnered with UWCCC hematologist and researcher Fotis Asimakopoulos on this project, building upon Asimakopoulos’ previous work on versican and versikine, two related proteins which seem to influence the inflammation and immune response surrounding certain types of cancer.

While versican has been found to worsen the immune response to myeloma — a cancer of the body’s plasma cells — its derivative, called versikine, has a more beneficial effect.

“Cancers have been characterized as wounds that do not heal, and versican contributes to this condition by accumulating at cancer sites, sustaining inflammation and blocking the immune system from fighting the cancer,” Asimakopoulos said. “Versican’s processing into versikine does the opposite in myelomas.”

Working together to study 122 samples of serious colon cancer obtained by the Carbone Center’s BioBank, Deming, Asimakopoulos and members of their teams used staining techniques to search for versican and versikine.

They found that cancerous areas had higher levels of versican, while healthy tissue around the tumors had higher levels of versikine. They also found that if versikine levels were higher in the tumor, more T cells would infiltrate the tumor site — a good thing for patients.

Still, the researchers had to go a bit deeper to determine if versican processing into versikine was actually increasing the number of T cells at the cancer sites. To do so, they treated immune cell precursors with versikine, and found that a class of cells called Batf3 dendritic cells increased in number.

“This subset of dendritic cells is key for the success of all the immunotherapies that we commonly talk about, and these cells both educate the T cells by showing them the tumor antigens and invite the T cells into the tumor,” Asimakopoulos said.

Deming says this discovery could lead to better outcomes for cancer patients down the line.

“We’re excited about versikine as a biomarker to identify those patients for whom an immunotherapy strategy is best,” Deming said. “Also, can we manipulate this pathway that converts versican to versikine to enhance tumor responses to immunotherapies?”

Asimakopoulos added that studying the tumor microenvironment further will eventually lead to better analysis and treatments.

“Every tumor has a matrix, and the matrix is a living, dynamic structure that responds to the needs of the physiology of the growing tumor; sometimes it works against the tumor, sometimes it enables tumor growth,” he said. “We need to understand how the matrix influences tumor behavior so that we can find ways to make this immunotherapy revolution applicable to more patients.”

Deming and Asimakopoulos co-authored the study, which was published recently in in the Journal of Immunology. It was funded in part by the National Institutes of Health and the American Cancer Society.

See an earlier story on cancer research and treatment: http://wisbusiness.com/index.Iml?Article=387923

–By Alex Moe