Researchers gain new understanding of vaccine-resistant cancers

By Ruth SoRelle, M.P.H.

Breast and prostate cancer have proven particularly resistant to immune therapy treatments, and now a Baylor College of Medicine researcher thinks he may know why.

These tumors have a higher percentage of gamma delta T-cells than many other cancers, said Dr. Rong-Fu Wang, a professor in the BCM Center for Cell and Gene therapy in a report that appears in the journal Immunity. These cells suppress the cancer-fighting potential of the immune system. That could explain the ineffectiveness of vaccines in those diseases. The cells are part of the innate, or non-specific, immune system.

Cells potently suppress immune system

"Many epithelial cell-derived cancers such as those of the prostate and breast may contain high percentages of the gamma delta T-cells," said Wang. "Those gamma delta T-cells can potently mediate immune suppression and that causes the problem."

By contrast, he said, few of these T-cells are found in melanoma, a cancer that is receptive to treatment with cancer vaccines or immunotherapy.

Can suppressive effect be reversed?

An important question, he said, is how to overcome the suppressive effect these cells have on the immune system. One strategy would be to use ligands (small strands of genetic material) that bind to human Toll-like receptor 8 to reverse the suppressive function of tumor-infiltrating gamma delta T-cells.

Wang and his colleagues used such ligands to reverse the suppressive effects of CD4+ regulatory T cells, another group of T-cells that mediate important immune regulation in a previous study. They found that the same ligand reverses the suppressive effect of tumor-infiltrating gamma delta T-cells as well.

"We showed that the suppressive function of these gamma delta T-cells can be reversed by the same mechanism controlled by human Toll-like receptor 8 signaling pathway," he said.

New cancer-fighting strategies

Because he has identified a new type of immune cells that suppresses the ability of the immune system to fight breast and prostate cancer, Wang knows he has uncovered a new feature of how host immune cells interact with tumor cells. He said a better understanding of the interplay between immune cells and tumor cells will be the key to devising new strategies for cancer immunotherapy.

Using the same ligand or strand of genetic material could reverse the suppressive effects of both kinds of regulatory T-cells on the cancer-fighting immune system and may be a new avenue of treatment to pursue in the future, he said.

Others who took part in the research include: Drs. Guangyong Peng, Helen Y. Wang, Weiyi Peng, Yukiko Kiniwa and Kook Heon Seo, all of BCM.

Funding for this work came from the American Cancer Society, the Cancer Research Institute and the National Institutes of Health.