Northwestern Events Calendar

Dec
8
2020

M-I Dept. Virtual Seminar -Imaging-Driven Discovery of a CTLA-4-Dependent Feedback Loop that Controls T Regulatory Cell Abundance in Tumors

When: Tuesday, December 8, 2020
12:00 PM - 1:00 PM  

Where: Online

Audience: Faculty/Staff - Post Docs/Docs - Graduate Students

Contact: Dr. Booki Min   312.503.1805

Group: Department of Microbiology-Immunology Seminars/Events

Category: Lectures & Meetings

Description:

Title:

Imaging-Driven Discovery of a CTLA-4-Dependent Feedback Loop that Controls T Regulatory Cell Abundance in Tumors

Speaker: Francesco Marangoni, PhD / University of California, Irvine

Host: Booki Min, DVM, PhD

Topic:

Although checkpoint blockade immunotherapy extends overall and progression-free survival for some oncologic patients, its efficacy is still limited to a minority of cases and of tumor types. We hypothesized that immunotherapy failure can at least in part be ascribed to the functional enhancement of tumor-associated T regulatory cells (Treg). We characterized the spatio-temporal dynamics of antigen-mediated Treg activation in tumors using intravital microscopy, and discovered that CTLA-4 blockade directly enhances the activation and proliferation of tumor-associated Treg. Mechanistically, anti-CTLA-4 antibodies disrupt a CD28-dependent feedback loop that adjusts Treg proliferation to the amount of co-stimulatory ligands expressed in the tumor microenvironment. Inhibition of Treg activation greatly enhanced the therapeutic efficacy of CTLA-4 blockade. We thus discovered unwanted immunosuppression triggered by CTLA-4 blockade that may explain the lack of therapeutic efficacy in many patients.
 

 

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