02226nas a2200133   4500008004100000245012600041210006900167260000800236490000700244520167200251100002001923700002101943856012801964       2018                        eng d00a Exploring immuno-regulatory mechanisms in the tumor microenvironment: model and design of protocols for cancer remission0 aExploring immunoregulatory mechanisms in the tumor microenvironm  cSEP0 v133 aThe tumor microenvironment comprising of the immune cells and cytokines acts as the 'soil' that nourishes a developing tumor. Lack of a comprehensive study of the interactions of this tumor microenvironment with the heterogeneous sub-population of tumor cells that arise from the differentiation of Cancer Stem Cells (CSC), i.e. the 'seed', has limited our understanding of the development of drug resistance and treatment failures in Cancer. Based on this seed and soil hypothesis, for the very first time, we have captured the concept of CSC differentiation and tumor-immune interaction into a generic model that has been validated with known experimental data. Using this model we report that as the CSC differentiation shifts from symmetric to asymmetric pattern, resistant cancer cells start accumulating in the tumor that makes it refractory to therapeutic interventions. Model analyses unveiled the presence of feedback loops that establish the dual role of M2 macrophages in regulating tumor proliferation. The study further revealed oscillations in the tumor sub-populations in the presence of T-H1 derived IFN-gamma that eliminates CSC; and the role of IL10 feedback in the regulation of T-H1/T-H2 ratio. These analyses expose important observations that are indicative of Cancer prognosis. Further, the model has been used for testing known treatment pro-tocols to explore the reasons of failure of conventional treatment strategies and propose an improvised protocol that shows promising results in suppressing the proliferation of all the cellular sub-populations of the tumor and restoring a healthy T-H1/T-H2 ratio that assures better Cancer remission.1 aGanguli, Piyali1 aSarkar, Ram, Rup  uhttps://library.ncl.res.in/content/exploring-immuno-regulatory-mechanisms-tumor-microenvironment-model-and-design-protocols