Checkpoint blockade has revolutionized cancer therapy and provided undeniable evidence that T cells can effectively attack and eliminate tumors. Despite these impressive effects, many patients still don’t respond, and numerous clinical trials are now testing novel approaches that combine checkpoint immunotherapies with other treatments, including chemotherapy and DNA damage response (DDR) modulators. Certain chemotherapies and DDR-targeting drugs have been shown to inhibit T cell activation, but the acute and direct effects of these drugs on tumor-killing T cells remain poorly understood at a molecular level.
Therefore, Dr. Carrie Lucas aims to characterize the molecular effects of DNA damaging agents and DDR modulators on human T cell signaling and activation and test their effects when combined with PD-1 immunotherapy in mouse tumor models. Overall, this work will provide important new insights since the effects of chemotherapies and DDR modulators are mostly studied only in the tumor cells and not in the immune cells that kill tumor cells. Thus, her work should inform the development of novel and effective combination therapies that build on the success of PD-1 checkpoint blockade and have potential to further improve cancer patient outcomes.
Projects and Grants
Intersection of DNA damage pathways with T cell signaling responses
Yale University | All Cancers | 2020
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