Blake Heath

Conference 2022 Live Talk


Talk title

Investigating regulatory mechanisms influencing oral cancer-intrinsic Type I interferon production and signaling


Authors and Affiliations

Blake R. Heath1,2, Wang Gong2,3, Luke Broses2,3, Hülya F. Taner2,4, Andriana Manousidaki5, Steven B. Chinn3,6, Shaoping Zhang7, Haitao Wen8, Eric Bartee9, James J. Moon1,3,10, Yuying Xie5, Yu Leo Lei 1,2,3,4,6,*

1. Graduate Program in Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
2. Department of Periodontics and Oral Medicine, University of Michigan, Ann Arbor, Michigan, USA.
3. University of Michigan Rogel Cancer Center, Ann Arbor, Michigan, USA.
4. Graduate Program in Oral Health Sciences, University of Michigan School of Dentistry, Ann Arbor, Michigan, USA
5. Department of Computational Mathematics, Science, and Engineering, Department of Statistics, Michigan State University, East Lansing, Michigan, USA.
6. Department of Otolaryngology-Head and Neck Surgery, University of Michigan Health System, Ann Arbor, Michigan, USA.
7. Department of Periodontics, University of Iowa College of Dentistry, Iowa City, Iowa, USA
8. Department of Microbial Infection and Immunity, Ohio State University, Columbus, Ohio, USA
9. Department of Internal Medicine, Division of Molecular Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131
10. Department of Pharmaceutical Sciences, University of Michigan College of Pharmacy, Ann Arbor, MI 48109




Cancers frequently disable STING-mediated type-I interferon (IFN-I) production to escape from innate immune surveillance. Cancer-specific STING competency maintains the immunogenicity of head and neck squamous cell carcinomas (HNSCC), which is among a few cancer types with an increasing incidence. Most HNSCCs are hypoimmunogenic and refractory to immunotherapy. Little is known about how underlying metabolic conditions regulate the immunogenicity of HNSCC.




We found that obesity created an IFN-I-deprived tumor microenvironment with a massive expansion of suppressive myeloid cell clusters and contraction of effector T-cells. Saturated fatty acids, but not unsaturated fatty acids, potently inhibited the STING-IFN-I pathway in HNSCC cells. Obese hosts exhibited significantly increased tumor burden and lower responsiveness to STING stimulation. As a mechanism, saturated fatty acids induced the expression of NLRC3, depletion of which resulted in a T-cell inflamed tumor microenvironment and IFN-I-dependent tumor control.


Overall, this work highlights a novel regulatory mechanism by which adiposity induces an innate immune sensor to drive cancer-intrinsic immunosuppression.