The Modeling And Analysis Of The Effect Of Mechanical Properties On Tumor Immune Response

Cancer is still considered the leading cause of death worldwide.The development and evolution of cancer involves complex processes that span multiple spatial and temporal scales between multiple cell populations and the extracellular environment.The immune system is a key regulator of tumor biology,an important system of immune response and immunoreaction.It can support or inhibit tumor development,growth,invasion and metastasis.However,the low immune properties of tumor cells result in the ability of tumor cells to effectively evade recognition and clearance by the immune system.Therefore,by studying the factors that influence the interaction between tumor and immune system,three states of tumor immune system are understood: tumor is cleared by immune system,tumor and immune system reach balance state,and tumor cells escape.So far,many studies have designed mathematical models and experiments to describe the biological mechanisms that affect tumor growth and the tumor immune system.The results show that the growth and progression of tumor are closely related to the mechanical properties of cells and tumor microenvironment.Changes in extracellular matrix stiffness,intercellular adhesion,and immune checkpoints are often associated with the development and spread of a tumor.In this paper,a mathematical Model based on the Cellular Potts Model is developed to study the influence of the mechanical properties of cells on the development of tumor and the interaction between tumor and adaptive immune system.In the second chapter,we studied the effect of dynamic changes of extracellular matrix on the adhesion between tumor cells and matrix by establishing cell stiffness model and cell-ECM adhesion model,the simulation results show that the migration rate of tumor cells is dependent on the ECM stiffness,and the increase of ECM stiffness promotes the migration of tumor cells in low stiffness.But on the ECM with greater stiffness,tumor cells need to accumulate a sufficient amount of integrin,and the increased expression of integrin will increase the surface tension and cell-ECM adhesion energy.Therefore,a further increase in ECM stiffness inhibits tumor cell migration.In chapter 3,we added a tumor immune response model to establish the interaction between tumor cells and immune cells by integrating tumor cell progression and immune development,the model was used to investigate how immune checkpoints affect cell-cell interactions and how changes in cell-cell adhesion affect tumor immune response.The results show that CTLA-4,an immune checkpoint,affects the adhesion between cells by acting on the downstream signaling pathways of T cells,which is conducive to the occurrence of tumor cell immune escape.