Scientists identify cell defects that limit immune system's impact on late-stage tumors

LOS ANGELES (Jan. 21, 2004) Although vaccines developed to help the immune system fight tumors appear to have an impact against early-stage tumors, they have little if any success in slowing the growth of tumors in later stages. Now researchers writing in the Feb. 1, 2004 issue of The Journal of Immunology identify abnormalities in the immune system's T cells, provide insight into their origin, and describe how these defects can be prevented and "repaired" in animal experiments.

"Conventional thinking and previous studies suggest that the tumor environment is responsible for immune dysfunction in cancer-fighting T lymphocytes that congregate at the site of a tumor. The major unresolved question is the origin and mechanism responsible for immune dysfunction in tumor-infiltrating T cells. We found that damaged T cells arose from a particular cell lineage, within a tumor environment that lacks factors promoting their survival," said Keith L. Black, MD, director of Cedars-Sinai's Maxine Dunitz Neurosurgical Institute, where the mouse studies were conducted. "Furthermore, we were able to influence the cells in a way that decreased the number of dysfunctional cells, a finding that we hope may eventually lead to more effective vaccine therapies against established tumors."

In a localized immune response, T cells are mobilized to attack cells that the immune system recognizes as invaders. Because specific lymphocytes recognize and attack specific immune threats, they are called "antigen-specific." In cancer vaccine experiments, such as those ongoing at the Institute to improve treatment for brain tumors, researchers seek to improve the immune response by helping cancer-fighting cells identify tumor cells as potential targets.

T cell activation is considered a major defense mechanism in the prevention of tumor formation, and in rodent studies T cell responses have been able to eradicate recently established tumors. In both humans and animals,

Contact: Sandra Van
Cedars-Sinai Medical Center

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