Seminario de Física Teórica ICIMAF
Lugar: ICIMAF, Calle E esq a 15, Vedado
Fecha: Viernes 27 de Marzo, 2pm
Ponente: Karina García (CIM)
Titulo: How Regulatory T cells impinge on Tumor Immunobiology?
Resumen: Aiming to get a better insight on the impact of regulatory CD25+CD4+ T cells in tumor-immunobiology, a simple mathematical model was formulated and studied. This model is an extension of a previous model for the dynamics of autoreactive regulatory cells and effector cells that interact upon their co-localized activation at the antigen presenting cells (APCs). It assumes that tumor growth stimulates the activation and migration to the adjacent lymph node of fresh APCs loaded with tumor antigens. These APCs stimulate the growth of both Effector and Regulatory T cells, which may then migrate to the tumor site and induce tumor cell destruction. Our results predict the existence of two alternative dynamic modes of unbounded tumor growth. In the first mode, the tumor induces the expansion of Effector T cells that outcompete regulatory T cells, but nevertheless fail to control the tumor. In the second mode, the tumor induces a balanced expansion of both Effector and Regulatory T cells, which prevents the tumor from being destroyed by the immune cells. Tumors characterized by a high specific growth rate, low immunogenicity, and that are relatively resistant to T cell destructive functions, will grow in the first mode; conversely, tumors that have a slow specific growth rate, that are immunogenic, and/or that are more sensitive to destruction by T cells will grow in the second mode. Overall this results provides a simple explanation to the observation that the development of some tumors expand regulatory T cells while others do not, predicting how some key dynamical properties of the tumor determine either one or the other type of behavior.
We study how these two tumor classes respond to different therapies, namely vaccination, immune suppression, surgery, and different combinations.. We show 1) how the timing and the dose applied in each particular treatment, determine whether the tumor will be rejected, with or without concomitant autoimmunity, or whether it will continue progressing with slower or faster pace; 2) that both regulatory T cell dependent and independent tumors are equally sensitive to vaccination, although former are more sensitive to T cell depletion treatments and are unresponsive to partial surgery alone; 3) that surgery, suppression, and vaccination treatments, can synergistically improve their individual effects, when properly combined. Particularly, we predict rational combinations helping to overcome the limitation of these individual treatments on the late stage of tumor development.