More than 500,000 people have received a transplanted organ in the United States and 27,000 additional transplants are performed each year. Solid organ transplant recipients are 100-times more likely to develop cutaneous squamous cell carcinomas (SCCs) than the general population. As immunosuppression used after transplantation focuses on impairing T cell activation, a majority of studies on the etiology of post-transplant skin cancers has focused on the loss of cancer immunosurveillance. However, we have recently determined that the innate immune system is also critical in tumorigenesis. Further, increased numbers of macrophages present near tumors correlate with poor prognoses in approximately 80% of tumors. To date, few studies have characterized the mechanistic role of macrophages in the progression of SCCs.
We have developed in vitro and murine model systems to screen and verify soluble tumor-derived factors that activate macrophages to become tumor promoting. Our objectives are to identify and verify tumor-promoting factors produced by tumor-associated macrophages isolated from human SCCs from immunosuppressed transplant recipients and non-immunosuppressed patients. Characterizing the core elements of these tumor-promoting pathways is critical to identifying targets and abrogating them to prevent tumor progression and metastasis of SCCs both in this high-risk population as well as for the general population.
Colegio Lab Leadership