Marlies Meisel
University of Pittsburgh, PA·Microbiology & Immunology
Immunotherapy has transformed cancer treatment, but most patients do not respond to it. One class of these drugs, immune checkpoint inhibitors, releases the brakes on killer T cells so they can attack tumors.
- Fields
Microbiology & Immunology
Medicine & Clinical Research
Physiology
- Topics
cancer immunotherapy
immune checkpoint inhibitors
melanoma
- Grants
- 2 known grants, through Jun 2031
What they work on
- Test whether checkpoint-inhibitor-response-associated gut bacteria convert dietary tryptophan into molecules that activate the aryl hydrocarbon receptor (AhR) and strengthen interferon-gamma-producing Tc1 CD8 T cells, in cell culture.
- Determine whether AhR-ligand-producing bacteria improve checkpoint inhibitor efficacy through AhR-dependent and AhR-independent signaling inside CD8 T cells, using both therapy-sensitive and therapy-resistant mouse melanoma models.
- Test whether aerobic exercise enhances antitumor CD8 effector T cell immunity and improves cellular and checkpoint inhibitor therapy by way of gut microbiota-derived metabolites, in mouse melanoma models.
- Define how CD8 T cells sense exercise-induced microbiota metabolites, including the receptor involved, and test probiotic approaches that promote these metabolic pathways to boost immunotherapy response.
More about the research
Strikingly, which bacteria live in a patient's gut helps decide whether these drugs work, and so does whether the patient exercises. The research program asks how those two outside factors reach the immune system. Both projects converge on the same cell type: CD8 T cells that make the inflammatory signal interferon-gamma, called Tc1 or CD8 effector cells. The shared hypothesis is that gut bacteria convert dietary molecules into small chemicals, metabolites, that travel through the body and push these T cells into a stronger antitumor state. Melanoma, an aggressive skin cancer, is the main model.
Why it matters
Most cancer patients do not benefit from immune checkpoint inhibitors. By identifying the specific gut bacteria, metabolites and T cell receptors that strengthen antitumor immunity, this work could support microbial-based precision cancer therapeutics, such as defined probiotics or metabolite supplements, that make existing immunotherapy work for more patients with melanoma and other cancers. It may also explain why exercise improves cancer outcomes, giving a biological basis for prescribing it alongside treatment.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
John Mountz
University of Alabama at Birmingham, AL·Microbiology & Immunology
Determine which IL-4-induced tryptophan metabolic signals block TLR7-driven autoantibody-precursor B cells in vivo, comparing wild-type mice with mice lacking the B-cell enzymes IL4i1 and Ido1 or the metabolite sensor AhR.
Joel S Greenberger
University of Pittsburgh, PA·Medicine & Clinical Research
Test whether the engineered probiotic LR-IL-22 restores gene transcription suppressed by irradiation in Lgr5+GFP+ intestinal crypt stem cells, the fluorescently labeled cells that regenerate the gut lining.
Carrie Daniel-MacDougall
University of Texas MD Anderson Cancer Center, TX·Medicine & Clinical Research
Test whether a prebiotic food-enriched diet (PreFED), delivered as prebiotic foods plus nutrition counseling, changes the gut microbiome and blood metabolites of metastatic melanoma patients receiving checkpoint inhibitor immunotherapy.
The school
University of Pittsburgh: 83 labs on PI Pages, $1.5B a year on research, 403 research doctorates a year.
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