Cytotoxic T cell function in solid tumors: principles and implications for immunotherapy

Abstract

Activation of the immune system, the body’s own anti-cancer defense, is a promising approach for a range of cancer types with the potential to raise a specific, adaptive and long-lasting anti-cancer protection. In this thesis novel in vitro models which mimic the 3D tissue organization and in vivo imaging approaches were developed to visualize immune effector cells (cytotoxic T cells, CTL) within live melanoma lesions. As novel imaging modality in cancer research, third harmonic generation (THG) microscopy was established for label-free visualization of tissue structures. Monitoring CTL function at single-cell level shows how CTL cooperate to kill tumor cells and how an immune-modulatory antibody (a-CD137) enhances CTL efficiency. In summary, in this thesis kinetic imaging and intravital microscopy were applied to deepen the mechanistic understanding of immune cell function within complex tissues which forms the basis for improved, rationale design of immunotherapies