Researchers from the Medical College of Cornell and the Rockefeller University will attempt to determine whether, in patients who receive a transplanted organ, certain of their immune cells actively suppress their immune system from responding to squamous cell carcinoma of the skin, allowing the potentially deadly tumor to rapidly grow.
Prior to transplantation, patients receive medication to reduce their immune system’s ability to attack the donated organ. This weakened immune response makes transplant recipients highly vulnerable to opportunistic infections. Additionally, a majority of transplant recipients develop an aggressive form of squamous cell carcinoma of the skin, which is the second most prevalent type of human cancer. The researchers suspected that the high incidence and aggressiveness of this cancer in transplant patients, often a deadly situation, was due to a reduced ability of their immune cells to conduct vigilant surveillance of potentially harmful agents. Preliminary evidence, though, suggests that this is not the whole story.
Instead, according to the researchers, patients’ innate immune “dendritic cells,” the body’s sentries, may recognize the cancer, but their responses may be suppressed by regulatory”immune T cells that ordinarily prevent immune responses to harmless agents. The resultant immune tolerance to the cancer would enable its rapid growth. Researchers will now test this hypothesis by further comparing immune responses to the cancer in transplant and non-transplant patients. Skin biopsies from patients in each of the two cancer groups will be compared to identify: 1) characteristics of the patients’ immune regulatory T cells and dendritic cells; 2) functions of these cells in response to the cancer; and 3) properties of the cancer cell that dendritic cells initially recognize, so that methods could be developed to strengthen that response so that regulatory T cells could not suppress it.
Significance: The findings ultimately may lead to development of potentially life-saving treatment for transplant recipients who develop squamous cell carcinoma, in which immune cells would attack the cancer but not the transplanted organ.