Theresa Guo
University of California-San Diego, CA·Medicine & Clinical Research·Early-career
Immunotherapy drugs that release the brakes on the immune system are now a first-line treatment for head and neck cancer that has come back or spread. Yet fewer than 1 in 5 patients with head and neck squamous cell carcinoma (HNSCC), a cancer of the lining of the mouth and throat, respond to them.
- Fields
Medicine & Clinical Research
Microbiology & Immunology
Genetics
- Topics
head and neck squamous cell carcinoma
oral cancer
head and neck cancer
- Grants
- 1 known grant, through Aug 2029
What they work on
- Predict and rank splice-variant-derived peptides, short protein fragments made only by tumors with abnormal RNA splicing, from head and neck squamous cell carcinoma using an established computational pipeline.
- Test which predicted splice-variant peptides trigger an immune response, using an immunocompetent mouse model of oral cancer in which the mice have a working immune system.
- Build the immune-activating splice-variant peptides into a tumor vaccine. Test whether it helps oral tumors in mice respond better to immune checkpoint inhibitors, drugs that release the immune system's brakes.
- Measure immune responses to human splice-variant neoantigens in oral cancer patients to assess whether these vaccine targets could be used in the clinic.
More about the research
One way to improve this is a tumor vaccine. Such a vaccine would train the immune system to recognize neoantigens, which are protein fragments found only on cancer cells. Most known neoantigens come from DNA mutations. This project looks at a less-studied source: alternative splicing. Splicing is the step where a gene's message is cut and rejoined before it is made into protein. When it goes wrong in tumors, it can produce abnormal proteins that the immune system may see as foreign.
Why it matters
Fewer than 20% of patients with recurrent or metastatic head and neck cancer benefit from immune checkpoint inhibitors. Vaccines built from splice-variant neoantigens could boost the immune system and raise these response rates. The approach could add a new, previously unrecognized class of targets for head and neck cancer vaccines. It may also extend to other solid tumors whose cells vary widely from one another.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Xiao-Jing Wang
University of Colorado Denver/Anschutz Medical Campus, CO·Medicine & Clinical Research
Test whether blocking TGFβ and PD-L1 together strengthens the radiation-triggered "in situ vaccine" effect and immune activation across the body, using mouse oral cancer cells transplanted into the mouth of immune-competent mice.
Sana D Karam
Washington University in St Louis, MO·Microbiology & Immunology
Determine how immune checkpoint inhibitors such as anti-PD-L1 drugs act on PD-1-expressing regulatory T cells and their STAT3 signaling during radiation therapy, using genetically engineered mice and samples from HNSCC clinical trials.
Dohun Pyeon
Michigan State University, MI·Microbiology & Immunology
Define how the chemokine CXCL14 increases MHC-I antigen presentation, which lets immune cells recognize tumor cells, to suppress HPV-positive head and neck squamous cell carcinoma.
The school
University of California-San Diego: 84 labs on PI Pages, $1.9B a year on research, 637 research doctorates a year.
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