Yumeng Mao – Dissecting the negative immune regulatory network to improve cancer immunotherapy

The research group focuses on developing cancer immunotherapy, with the specific goal to reveal functionally meaningful resistance mechanisms against immune checkpoint inhibition in cancer patients. Given the progress and challenges of cancer immunotherapy in the clinic, our work has the potential to reveal insights for novel therapeutic concepts.

Cancer immunotherapy has in recent years emerged as a very promising treatment strategy. With the rapid development of cancer immunotherapy in the clinic, there is a great need to gain in-depth understanding of the resistance mechanisms to therapy. The goal of our studies is to determine the negative feedback network for anti-tumour immune responses in the tumour microenvironment, with a special interest in rare cancer types where immunotherapy is less explored, e.g. childhood solid cancers.

More specifically, our research focuses on ways to overcome resistance mechanisms against the PD-1/PD-L1 blockade therapy in cancer patients. In one project we analyse the functional contribution of every single gene in the entire human cancer genome to the response of immune checkpoint blocking antibodies using CRISPR/Cas9 technology. We will also investigate negative checkpoints in myeloid cells using a novel CRISPR KO mouse model and in vitro primary human immune cell assays, in order to revert immune tolerance that confers resistance to immunotherapy.

Another project concerns the ‘cross resistance’ concept, where chemotherapy resistant human cancer cells may be less sensitive to immune-mediated killing after treatment with checkpoint blocking antibodies. We will further validate and dissect the mechanistic insights of the ‘cross resistance’ theory in human cancer cells using the CRISPR/Cas9 precise genome editing technology.