how might tumor initiating cells hijack stem cell features to evade immunotherapy?

Cancer treatments have been revolutionized by the development of immunotherapies but the treatment is still ineffective in far too many patients.  Dr. Miao hopes to identify new targets driving cancer immune resistance in skin cancers by building on the recent discovery of a special group of tumor cells with strong tumor initiating activities.  These cells, called Tumor Initiating Cells (TICs,) appear to have unique capacities to orchestrate immune cell activities. Dr. Miao will focus on a group of TICs that closely resemble adult tissue stem cells and that are able to withstand robust antigen-specific cytotoxic T-cell treatment. These TICs seem to be able to re-work the immune system,  much in the same way that normal skin cells exhibit an ability to modulate the immune system when healing a wound.  This capacity may help the TICs interact with the immune system and drive cancer immune evasion during tumorigenesis and may also be a primary cause of cancer recurrence after immunotherapy.

Dr. Miao has created a powerful new ultrasound-guided in utero microinjection technique to establish a novel immuno-oncology model in mice that will allow him to rapidly manipulate TIC/immune cell interactions in spontaneous tumors. Dr. Miao will use this platform to systematically map how the tumor microenvironment is organized and how it evolves over time, elucidate how TICs achieve and leverage their immunosuppressive abilities, determine the major TIC-specific factors responsible for sculpting the immunological niche that TICs employ, and figure out whether these TIC-immune system interactions can be targeted for immunotherapy. TICs are key forces driving cancer resistance after immunotherapy and Dr. Miao plans to provide a strong foundation for the development of new antibody or small molecule-based treatments to combine with current immunotherapies, maximizing their efficacy and preventing cancer reoccurrence. This study has the potential to reveal new cancer targets for the next generation of cancer immunotherapies.