Quantitative Approach to Explore Regulatory T Cell Activity in Immuno-Oncology

Abstract

The failure of immunotherapies in cancer patients is being widely studied due to the complexitiespresent in the tumor microenvironment (TME), where regulatory T cells (Treg) appear toactively participate in providing an immune escape mechanism for tumors. Therefore, therapies tospecifically inhibit tumor-infiltrating Treg represent a challenge, because Treg are distributedthroughout the body and provide physiological immune homeostasis to prevent autoimmune diseases.Characterization of immunological and functional profiles could help to identify the mechanismsthat need to be inhibited or activated to ensure Treg modulation in the tumor. To addressthis, quantitative in silico approaches based on mechanistic mathematical models integrating multiscaleinformation from immune and tumor cells and the effect of different therapies have allowedthe building of computational frameworks to simulate different hypotheses, some of which havesubsequently been experimentally validated. Therefore, this review presents a list of diverse computationalmathematical models that examine the role of Treg as a crucial immune resistance mechanismcontributing to the failure of immunotherapy. In addition, this review highlights the relevanceof certain molecules expressed in Treg that are associated with the TME immunosuppression,which could be incorporated into the mathematical model for a better understanding of the contributionof Treg modulation. Finally, different preclinical and clinical combinations of molecules arealso included to show the trend of new therapies targeting Treg.