Susan M. Kaech, Ph.D., CLIP Investigator Salk Institute for Biological Studies

Checkpoint immunotherapies, which revitalize our immune system’s ability to attack cancer, represent a breakthrough in cancer treatment. However, the majority of patients do not respond or their cancer progresses months after initially responding to therapy. A few patients on the other hand, are ‘exceptional responders’ who experience complete cures with tumors melting away within months. In order to find a “true” cure for cancer, it is critical to understand why some patients’ tumors completely regress and others do not. Dr. Kaech’s project will address this question in a way that has not been investigated before by comparing the immune responses induced between ‘exceptional responders,’ ‘progressors,’ and ‘non-responders.’

By definition, tumors are created by mutations that allow it to outgrow normal tissue. These mutations create mutated proteins known as ‘neoantigens’ that can potentially be targeted by the immune system. Many have tried to identify biomarkers that correlate with positive patient outcomes, but no study has systematically compared the number or quality of tumor-targeting T cells across these groups and correlated their abundance and quality with clinical outcome. Dr. Kaech, in collaboration with Dr. Roy Decker of Yale University, has collected blood samples from more than 60 patients with metastatic lung cancer who were treated with checkpoint immunotherapy and varied in their responses. Importantly, these samples were taken at various time points and her lab has cryopreserved many T cells from each patient so that they can be analyzed between patients with different outcomes. Overall, her study aims to study the differences in the neoantigen-specific T cell responses between ‘exceptional responders’ and ‘non-responders,’ in order to identify clues that could aid the design of more effective immunotherapy strategies.

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