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 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.
Group members
Publications
Epigenetic regulation of cell state by H2AFY governs immunogenicity in high-risk neuroblastoma
Part of Journal of Clinical Investigation, 2024
- DOI for Epigenetic regulation of cell state by H2AFY governs immunogenicity in high-risk neuroblastoma
- Download full text (pdf) of Epigenetic regulation of cell state by H2AFY governs immunogenicity in high-risk neuroblastoma
Part of Nature Communications, 2024
- DOI for Loss of NEDD8 in cancer cells causes vulnerability to immune checkpoint blockade in triple-negative breast cancer
- Download full text (pdf) of Loss of NEDD8 in cancer cells causes vulnerability to immune checkpoint blockade in triple-negative breast cancer
Part of Journal of Clinical Investigation, 2023
- DOI for Interleukin-1 receptor-associated kinase-3 acts as an immune checkpoint in myeloid cells to limit cancer immunotherapy
- Download full text (pdf) of Interleukin-1 receptor-associated kinase-3 acts as an immune checkpoint in myeloid cells to limit cancer immunotherapy
Part of Oncoimmunology, 2021
- DOI for Cisplatin inhibits frequency and suppressive activity of monocytic myeloid-derived suppressor cells in cancer patients
- Download full text (pdf) of Cisplatin inhibits frequency and suppressive activity of monocytic myeloid-derived suppressor cells in cancer patients
Part of Frontiers in Immunology, 2021
- DOI for Editorial: NK-Myeloid Cell Interactions in the Tumor Microenvironment: Implications for Cancer Immunotherapy
- Download full text (pdf) of Editorial: NK-Myeloid Cell Interactions in the Tumor Microenvironment: Implications for Cancer Immunotherapy
Phosphodiesterase 4A confers resistance to PGE2-mediated suppression in CD25(+)/CD54(+) NK cells
Part of EMBO Reports, 2021
- DOI for Phosphodiesterase 4A confers resistance to PGE2-mediated suppression in CD25(+)/CD54(+) NK cells
- Download full text (pdf) of Phosphodiesterase 4A confers resistance to PGE2-mediated suppression in CD25(+)/CD54(+) NK cells
Discovery of PROTAC molecules that selectively degrade the IRAK3 pseudokinase
Part of Journal of Medicinal Chemistry, p. 10460-10473, 2020
Part of Cancer Immunology and Immunotherapy, p. 1391-1401, 2020
- DOI for Human ovarian cancer intrinsic mechanisms regulate lymphocyte activation in response to immune checkpoint blockade
- Download full text (pdf) of Human ovarian cancer intrinsic mechanisms regulate lymphocyte activation in response to immune checkpoint blockade
Part of Current Medicinal Chemistry, p. 5654-5674, 2020
What industry can teach academia
Part of Science, p. 1342-1342, 2019