Carla V. Rothlin, Ph.D., CLIP Investigator Yale University

An important advance in treating cancer came from the recognition that the immune system can kill cancer cells. T cells are an essential component of the immune system that can kill tumors or help other immune cells attack the tumor. T cells exist in a “resting” naïve state, but once they receive the information of an infection or a tumor they can be “activated” to acquire the effector functions required to eliminate the infectious agent or the transformed cell. Dr. Rothlin has discovered that the “resting” state of naïve T cells, prior to activation, is heterogenous. More importantly, the potential of T cells to respond and become “activated” appears to depend on their resting state, with some states being more ready to respond than others. In this proposal Dr. Rothlin aims to (1) identify the triggers that induce naïve T cell heterogeneity and (2) establish the relationship between each naïve T cell state and their ability to mount an anti-tumor response in pre-clinical mouse models. The studies proposed will provide the foundation for assessing naïve T cell heterogeneity in humans. It is tempting to speculate that the distribution of naïve T cells into distinct states is variable across individuals and that those individuals with an increased proportion of more “readily activatable” T cell states display more favorable anti-tumor T cell responses and/or responses to immunotherapies.

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