Immune Function Clarified In Post-Transplant Cancer
Studies in mice are shedding new light on the intricate behavior of the body's immune system following solid organ transplant, a time when patients are exceptionally vulnerable to developing life-threatening infections and disorders.
Following transplant surgery, patients almost always have to take powerful drugs to suppress their immune systems. If they didn't, their bodies would reject their new organs. But the very same drugs that can save their lives may also jeopardize them, by blocking the activity of millions of white blood cells (called T cells) that normally fend off foreign invaders like bacteria, viruses, or even cancer.
The most common cancer among transplant patients is squamous cell carcinoma of the skin. "Squamous cell carcinoma of the skin occurs 60 to 250 times more frequently in transplant patients than in the general population," says Dr. Tatiana Oberyszyn, assistant professor of pathology in the Ohio State University College of Medicine.
Oberyszyn notes that while squamous cell carcinoma is often treated successfully in healthy people, it is frequently fatal in transplant patients.
When squamous cell cancer arises, two main types of T cells spring into action, CD4 cells and CD8 cells. Earlier studies suggested that CD8 cells (also known as killer T cells) were more important than CD4 cells in blocking tumor growth.
"Transplant patients who develop squamous cell carcinoma are at a definite disadvantage because the function of their CD4 and CD8 cells is dramatically altered by immunosuppressive drugs like cyclosporin and rapamycin," says Oberyszyn, who is also a member of the Ohio State University Comprehensive Cancer Center.
Transplant patients are also exquisitely sensitive to sunlight. Physicians normally advise them to avoid the sun following surgery, because the sun's ultraviolet radiation can lead to DNA damage and set the stage for malignant growth.
"Still, we know that lots of patients do venture outside unprotected because they feel so much better with their new organ, and they just want to be out and about," says Oberyszyn. "Under the circumstances, though, it's just very risky behavior."
Hoping to understand more fully the role of T cells in the development of squamous cell carcinoma, Oberyszyn and her colleagues, Drs. Donna Kusewitt and Anne VanBuskirk, designed the experiments in mice to mimic chronic sun exposure transplant patients might normally encounter.
The researchers eliminated CD4 cells from one set of mice and CD8 cells from another group. They then exposed some members of both groups to short-term UVB radiation and others to longer-term periods of ultraviolet B radiation. They measured various factors in the animals' immune response and noted tumor development in the mice that had the longer exposure.
Surprisingly, the researchers discovered that elimination of CD4 cells