Cancer Immunology

Over the past decade, the introduction of new cancer therapies that unleash a patient’s own immune system on their tumors has revolutionized how we treat many cancers, giving patients with cancers that would have been a death sentence 10 years ago, some factual hope of survival. Nevertheless, many patients still don’t respond to these immune therapies, highlighting the need for continued therapeutic development. With our lab's experience in mitochondrial metabolism and metabolic signaling, we set out to apply this knowledge to tumor immunology to better understand how perturbations in tumor metabolism could induce or help sustain immune responses.
 
In our first publication in this field, we found that deletion of two components of the mitochondrial oxidative phosphorylation complex I, induced strong immune-mediated anti-tumor effects. These effects were driven by increased expression of MHC class I antigen processing and presentation machinery. We found that these mutants had greatly increased mitochondrial acetyl-CoA, which through unknown mechanisms, seemed to be driving H3K27ac in the promotor regions of key MHC class I related genes. This cell intrinsic rewiring of metabolism and transcription drove increased T-cell activation and immunotherapy responsiveness in mouse melanoma models. 
 
We currently have several projects in the lab diving into metabolic regulation of immune cell activity both in cancer and rare disease models. We are currently growing this side of the lab and are actively recruiting immunologists interested in exploring the intersection between immunology and metabolism. 

Selected publications
 
Selective deficiency of mitochondrial respiratory complex I subunits Ndufs4/6 causes tumor immunogenicity
Jiaxin Liang*, Tevis Vitale*, Xixi Zhang, Thomas D. Jackson, Deyang Yu, Mark Jedrychowski, Steve P. Gygi, Hans R. Widlund, Kai W. Wucherpfennig, Pere Puigserver. Nat. Cancer. 17 January 2025. doi: 10.1038/s43018-024-00895-x