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

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 faces clinical challenges, e.g. childhood solid cancers, triple negative breast cancer.

Resistance mechanisms in immune checkpoint blockade therapy

More specifically, our research focuses on ways to uncover and overcome novel resistance mechanisms the immune checkpoint blockade (ICB) 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 clinically approved ICB drugs 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.

The cross resistance concept

Another project concerns the ‘cross resistance’ concept, where chemotherapy resistant human cancer cells may be less sensitive to immune-mediated activation by ICB drugs. 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.

Developing drug candidates

In a long term, we have the ambition to bring our novel scientific discoveries to drug candidates, through collaborations with the drug discovery and development platform and the innovation office at Uppsala University.