Immune checkpoint therapies that aim to (re)activate the immune response against cancer cells have shown promising results in a variety of tumor types. Yet, a large fraction of cancer patients does... Show moreImmune checkpoint therapies that aim to (re)activate the immune response against cancer cells have shown promising results in a variety of tumor types. Yet, a large fraction of cancer patients does not benefit from these therapies. While the presence of a substantial number of immune cells, and in particular T cells, in the tumor is generally related with a better clinical response to checkpoint therapies, the T cells in the tumor are diverse in their capacity to eliminate the tumor. In order to improve treatment outcome of cancer patients, we require a better understanding of the roles of different T cells in the response (and resistance) to immune checkpoint therapy. The development of single cell profiling technologies has provided us with a powerful tool to analyze the state and functionality of individual cells. In this thesis, I have used single cell profiling methods in combination with innovative experimental technologies to unravel the diversity of T cells in human tumors and define the changes in the profiles of T cells that occur in response to treatment with immune checkpoint therapy to dissect which T cells are important for therapy response. Show less
The breakthrough of immunotherapy for cancer has introduced promising new options, but nonetheless only a minority of cancer patients show significant clinical benefit. This situation has inspired... Show moreThe breakthrough of immunotherapy for cancer has introduced promising new options, but nonetheless only a minority of cancer patients show significant clinical benefit. This situation has inspired two avenues of research to find solutions to this problem: mechanistic studies to decipher the working mechanisms of immunotherapies and to investigate why many patients do not respond, and studies developing combination treatments to achieve clinical benefit in situations where immunotherapy alone is not sufficient. This thesis explores both these avenues by investigating applications of visible light in immunotherapy of cancer in pre-clinical models. We developed optical imaging platforms for visualization of immune cells and immunotherapies, which can shed light on the immunological events after administration of immunotherapy. In addition, we investigated novel therapies based on the combination of tumor ablation by Photodynamic Therapy and different types of immunotherapy. Our findings may prove useful in understanding success and failure of immunotherapy, and provide new combination treatment options when the efficacy of monotherapy is insufficient. Show less
