Hussein Sultan
Washington University in St Louis, MO·Microbiology & Immunology
Cancer vaccines made from neoantigens — protein fragments found only on a patient's tumor cells — can delay tumor recurrence in some people, but most do not benefit. One reason is that the same vaccines can switch on immune cells that hold the attack back.
- Fields
Microbiology & Immunology
Medicine & Clinical Research
Biology
- Topics
Tr1 cells
regulatory T cells
neoantigen cancer vaccine
- Grants
- 1 known grant, through Apr 2028
What they work on
- Determine how the EBI3 subunit of the suppressive cytokine IL-35 drives induction of Tr1 regulatory CD4 T cells, using IL-35 reporter mice in established tumor models to identify which cells produce it.
- Test whether neutralizing IL-35 reduces Tr1 suppression, reprograms CD4 T cells toward an inflammatory Th1 phenotype, and boosts CD8 killer T-cell responses and vaccine-driven tumor rejection.
- Define what controls expression of the IL-35 receptor chains IL-12Rβ2 and IL-27Rα on tumor-specific CD4 T cells, since both are required for Tr1 induction.
- Ask whether strong binding between peptide-MHC class II and the T-cell receptor favors Tr1 fate, by comparing vaccines containing altered peptide ligands with low MHC-II binding affinity against standard high-dose neoantigen vaccines.
More about the research
Type 1 regulatory T cells (Tr1) are suppressive helper T cells that lack Foxp3, the usual marker of regulatory T cells; Tr1-like cells show up in cancer patients and track with worse outcomes. Work here asks what makes these suppressive cells appear after vaccination and how to avoid them.
Why it matters
Neoantigen vaccines and checkpoint drugs such as anti-PD-1 help only a minority of cancer patients. Identifying what turns on suppressive Tr1 cells could point to vaccine designs — adjusted peptide doses or weaker-binding peptide variants — and to IL-35 blockade as a way to keep these brakes off, potentially improving responses to existing immunotherapies.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Yaoying Wu
Syracuse University, NY·Biomedical Engineering
Develop nanoparticles that encapsulate the immunosuppressant rapamycin and display proteins mimicking tolerogenic dendritic cells, including peptide-MHC class II plus inhibitory ligands such as PD-L1/2 and Fas ligand, for delivery to antigen-specific T cells.
Ellen Robey
University of California-Berkeley, CA·Microbiology & Immunology
Define the molecular links between different branches of T cell receptor (TCR) signaling and the transcription factor network that specifies the CD4 helper fate, guided by a high-resolution single-cell map of T cell development.
Peter Aidan Savage
University of Chicago, IL·Microbiology & Immunology
Define the biophysical and structural basis by which T cell receptors from regulatory and conventional CD4+ T cells recognize the same self-peptide displayed on MHC class II, testing whether a more centered binding mode increases signaling sensitivity.
The school
Washington University in St Louis: 97 labs on PI Pages, $1.2B a year on research, 365 research doctorates a year.
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