Monitoring of CD8(+) T-cell Activity in mTOR Inhibitor-treated Cancer Patients for Successful Immunotherapy

Abstract

Mammalian target of rapamycin (mTOR) inhibitors are strong anti-tumor drugs; however, they have adverse immunosuppressive side effects in some cancer patients. Animal studies have provided evidence that mTOR inhibitors improved tumor-specific T-cells adoptive transfer in which the quality of CD8+ T-cells is a major factor for predicting success. Interestingly, mTOR inhibitors are capable of stimulating cytotoxic CD8+ T-cell if their dose/duration is adjusted. Rapamycin-induced CD8+ T-cells have also been associated with tumor immunity in animal models. We hypothesize that mTOR inhibitors can be a potential tool toward successful immunotherapy in cancer patients. CD8+ T-cell activity should be monitored before and after treatment to identify patients with improved CD8+ T-cells who might further benefit from expanding these cells and autologous lymphocyte therapy. Patients with a suppressed CD8+ T-cell activity may require individual adjustment of the drug dose in order to convert harmful immunosuppressive side effects of mTOR inhibitors into helpful immunostimulastory activities. Further investigations and clinical trials are required to prove the utility of CD8+ T-cell monitoring for successful immunotherapy in mTOR inhibitortreated cancer patients.