Speaker
Description
Immunotherapeutic approaches that exploit and manipulate cellular immune responses have increased our ability to treat various malignant diseases. However, these approaches still have their limitations and tend to fail in numerous patients, requiring a more mechanistic and quantitative understanding about the complex, intermingled dynamics of cell migration, differentiation and turnover that regulate immune responses. Developing multi-scale population dynamics models and applying them to time-resolved murine and human data on immune dynamics in response to vaccination, as well as immunotherapeutic treatment by CAR-T cell therapies in patients suffering from diffuse large B-cell lymphoma (DLBCL), we determined how individual processes of cell migration, proliferation and differentiation interact to shape cellular immune responses. Our analyses suggest the existence of optimal time windows for therapeutic interventions and are able to recapitulate the dynamics of responders and non-responders to CAR-T cell therapy, suggesting the relation of individual T cell subset kinetics to therapy outcome and toxic side effects. This illustrates the necessity for a mechanistic and quantitative understanding of the individual processes that shape cellular immune responses on a systemic level in order to improve immunotherapeutic strategies.
