Fingolimod blocks immunosurveillance of myeloma and B-cell lymphoma resulting in cancer development in mice.

Fingolimod (FTY720, 2-amino-2-propane-1,3-diol hydrochloride) is a remarkably efficient immunosuppressive drug that was recently approved as the first oral treatment for multiple sclerosis. Fingolimod prevents lymphocyte egress from lymph nodes by targeting 4 of 5 sphingosine-1-phosphate receptors.1 Two phase 3 trials showed that fingolimod significantly reduced multiple sclerosis disease progression compared with placebo or standard treatment.2,3 However, both trials concluded that longer studies were required to assess possible long-term risks.2,3 Reports from studies in mice and humans strongly support a crucial role of lymphocytes and adaptive immunity in both preventing cancer and fighting established tumors in a process called cancer immunosurveillance.4,5 In transplant recipients, lifelong immunosuppressive treatment is associated with an increased risk of cancer.6 We investigated the effect of fingolimod on cancer immunosurveillance mediated by tumor-specific CD4 T cells in mouse models for myeloma and B-cell lymphoma. We used severe combined immunodeficient (SCID) mice made transgenic for a T cell receptor (TCR) that recognizes a tumor-specific idiotypic (Id) antigen that is secreted by MOPC315 myeloma and F9 B-cell lymphoma.7,8 The