Combining mTOR Inhibitors and T Cell-Based Immunotherapies in Cancer Treatment

Abstract

mTOR regulates several processes that control tumor development, including cancer cell growth, angiogenesis and the immune response to tumor. Accordingly, mTOR inhibitors have been thoroughly explored in cancer therapy but have failed to provide long-lasting anticancer benefits. Several resistance mechanisms that counteract the antitumor effect of mTOR inhibitors have been identified and have highlighted the need to use mTOR inhibitors in combination therapies. In this context, emerging evidence has demonstrated that mTOR inhibitors, despite their immunosuppressive properties, provide anticancer benefits to immunotherapies. In fact, mTOR inhibitors also display immunostimulatory effects, in particular by promoting memory CD8+ T cell generation. Hence, mTOR inhibitors represent a therapeutic opportunity to promote antitumor CD8 responses and to boost the efficacy of different modalities of cancer immunotherapy. In this context, strategies to reduce the immunosuppressive activity of mTOR inhibitors and therefore to shift the immune response toward antitumor immunity will be useful. In this review, we present the different classes of mTOR inhibitors and discuss their effect on immune cells by focusing mainly on CD8+ T cells. We further provide an overview of the different preclinical studies that investigated the anticancer effects of mTOR inhibitors combined to immunotherapies.