Study On The Multi-parameter Characterization Of The Behavior Of Immune Cell Movement In Tumor Microenvironment

Immune cells are more widely distributed than any other cell in the body,and migration is the basis of their immune function.The response of immune cells to pathogens usually requires long-term migration.In order to reveal the regulatory mechanism of the immune process,study the behavioral characteristics of immune cells,and provide more biological information for the diagnosis of diseases,it is very important to extract and process multi-dimensional data with frequency,time,and space domain which acquired from in vivo imaging.However,processing of massive data,and analyzing of the characteristics of cells behavior are the great challenges in the study of immune cells migration during the immune response.At present,more and more parameters are used to characterize cellular dynamics,and a single parameter cannot accurately characterize the behavior of cells movement.Based on the requirements of data analysis in our group,this thesis has established a complete set of analysis methods of cells dynamics,and it can realize the quantitative analysis of cells movement characteristics.Based on the established cellular dynamics multi-parameter analysis method,we used it to analyze the behavioral characteristics of immune cells in tumor microenvironment.By comparing the curves of instantaneous velocity and shape index,the correspondence between the two changes is demonstrated,indicating that the cell regulates the instantaneous velocity of migration by changing its own morphology.The scatter graph of instantaneous velocity and shape index were plotted.It was found that one shape index can correspond to multiple instantaneous velocities,and one instantaneous velocity can also correspond to multiple shape indices,suggests that the instantaneous velocity of immune cells in the process of migration is regulated by their own morphology and is also affected by their environment.In a short interval,the relative angular distribution of immune cells was U-shaped,indicating the directional persistence of immune cells movement in a short period of time.As the time interval increases,the relative angle distribution first deepens the U-shaped distribution,and then gradually tended to be flat,it indicates that the direction of cells movement does not affect each other during long intervals.The mean asphericity of the trajectory of immune cells did not differ between the immunized group and the non-immunized group.It is presumed that the shape of the trajectory is inherent to the cell.By comparing the motion of immune cells inside and outside the tumor,we found that the tumor-peripheral immune cells have obvious directional selectivity.Due to the interaction between tumor’s internal immune cells and tumor,all the parameters,such as average velocity,confinement ratio,arrested coefficient,the slope of MSD fitted line,indicate that the peripheral immune cells of the tumor are more active and directional than the immune cells in the tumor.According to the classical parameters of motion type,we plot MSD on a log-log axis,it grows with time approximately as t~α,αis 1.63,and not is 1,as expected for Brownian walk.The value ofαfalls within the range of 1<α<2,and it is believed that tumor-infiltrating immune cells follow the law of super-diffusion in the tumor microenvironment.