Rapamycin and Squamous Cell Carcinoma in Renal Transplant Recipients
Posted: Thursday, August 30, 2018
Renal transplant recipients who are given rapamycin instead of a calcineurin inhibitor such as tacrolimus appear to have a decreased risk of secondary squamous cell carcinoma and a regression of preexisting premalignant lesions, according to a study published in OncoImmunology. Rapamycin and other mTOR inhibitor regimens likely allow CD8-positive memory T cells to maintain some of their function, revealed James W. Wells, PhD, of The University of Queensland, Brisbane, Australia, and colleagues.
“Our findings may suggest that patients switched to mTOR inhibitor regimens may well benefit from enhanced CD8-positive memory T cell function to new antigen challenges in their skin, such as those induced through new [ultraviolet]-induced mutations,” stated Dr. Wells and colleagues.
The risk of squamous cell carcinoma in patients receiving immunosuppressant medications is greatly increased, with a rate of non-melanoma skin cancer that is 65 to 250 times higher than the general population. In this study, researchers found that unlike clinically relevant concentrations of tacrolimus in the blood, clinically relevant concentrations of rapamycin in the blood correspond to a relatively “low-dose” drug environment in the skin. This allowed the infiltration of CD8-positive effector memory T cells into ultraviolet-induced squamous cell carcinoma lesions and also enhanced the number and function of antigen-specific CD8-positive effector and central memory T cells in the skin.
“Our results advocate further study into the contribution that immune mechanisms may play in the reduced risk of [squamous cell carcinoma] development associated with rapamycin treatment,” concluded the investigators.