- This project is suitable for a highly motivated PhD student.
Cancer immunotherapy, which harnesses and enhances tumor-specific T cell responses, has become the new fourth pillar of cancer treatment (to surgery, radiotherapy and chemotherapy). Antibodies targeting the T cell immune checkpoint receptor PD1 or its ligand PDL1 alone or in combination with CTLA4, have demonstrated efficacy in more than 20 different cancer types, particularly where the tumor microenvironment (TME) contains T cells and PDL1. Anti-PD1/PDL1 are FDA-approved to treat many advanced cancers including metastatic melanoma and lung cancer due to their ability to promote long-term regression and potential cures2. New trials are testing the efficacy of a-PD1 or a-CTLA4 in earlier stages of cancer, particularly in an adjuvant setting following surgery to prevent recurrence of distant metastases. However, the scheduling and efficacy of immunotherapy combined with cancer surgery has not been systematically examined. Using pre-clinical mouse models of spontaneously metastatic cancers, our group recently demonstrated for the first time, that neoadjuvant immunotherapy and surgery is superior to surgery followed by adjuvant immunotherapy for eradicating metastatic disease and promoting long-term survival. This pre-clinical data was used by our clinical collaborators to initiate new comparative trials of neoadjuvant and adjuvant immunotherapy in melanoma with preliminary results validating our findings. However, the overall survival data from this and other neoadjuvant immunotherapy trials are several years away and the immunological mechanisms underlying neoadjuvant-treatment’s efficacy are not well understood. This project aims to understand the key mechanisms and/or pathways activated by neoadjuvant immunotherapy may allow for their selective targeting and further improve the efficacy of immunotherapies in general.
The project will concern research work in an international team of highly motivated scientists in the areas of cellular and molecular immunology, cancer biology, in experimental mouse models and human patient materials. Theoretical training in immunology is highly desirable. Technical skills in animal experimentation, bioinformatics, flow cytometry and/or cellular immunology are preferable.