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Mismatch Repair Immunotherapy Convergence Team

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Connecting Immune Health and Tumor Biology in Gynecologic Cancers

Team Leader

  • E. John Wherry, PhD

    Team Leader
    Director of the Institute for Immunology and Professor of Microbiology at the University of Pennsylvania
    + Full Bio

About This Team’s Research

Mismatch repair (MMR)-deficiency, the inability to repair base pairing within the DNA helix, can give rise to a weakened DNA structure which leads to the accumulation of mutations. The response to immune checkpoint inhibitors has been varied in gynecologic cancers, possibly due to the number of mutations carried by each tumor cell (mutational burden). The team hypothesizes that the tumors with a high mutational burden fail to respond to checkpoint inhibition because of an immune dysfunction which is based on the mechanism for the MMR deficiency. The team plans to initiate two clinical trials that will test whether a) tumor-intrinsic factors affect the response to checkpoint inhibition; b) baseline immune function and quality affects response to checkpoint inhibition; and c) on-treatment blood markers may reflect the tumor-immune interaction. Understanding the mechanism that leads to this phenomenon has the potential to dramatically impact those patients who do not respond to current treatments.

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