The research of Casey R. Ager, Ph.D., focuses on cancer immunology, particularly the development and validation of new combination immunotherapies for genitourinary cancers and other tumors.
Dr. Ager's research uses high dimensional spectral flow cytometry and other state-of-the-art immune profiling technologies. These technologies map the dynamics of tumor-immune co-evolution in preclinical models and clinical specimens.
Dr. Ager's research has discovered the fundamental drivers of productive versus nonproductive immune responses to cancer. His research involves the development of new cancer therapeutics and fuels designs of new clinical trials with physician-scientist partners at Mayo Clinic and across the country.
- Temporal atlases of antitumor immunity. Dr. Ager's research monitored new preclinical models and 40+ parameter spectral cytometry methods. These models map the composition and phenotypic characteristics of immune cells in tumors, draining lymph nodes and blood. This is done through the entirety of an antitumor immune response, down to 24-hour resolution.
In collaboration with clinical partners in the Department of Urology, Dr. Ager's research maps the immune contexture of human genitourinary cancers. These cancers are monitored through the lifespan of disease stages to better understand how baseline immunity influences tumor progression and susceptibility or resistance to immunotherapies.
- Rational drug sequencing: Time-resolved cancer immunotherapy. Combination immunotherapy regimens have entered clinical use but remain highly toxic and marginally effective relative to single agent therapies.
Dr. Ager's research has engineered a novel approach to combination immunotherapy. He leverages temporal atlases of antitumor immunity to synchronize drug delivery to target expression or time-resolved therapy.
In collaboration with clinical partners at Mayo Clinic, Dr. Ager's research validates these findings through innovative correlative studies on neoadjuvant clinical trials.
- Novel targetable vulnerabilities of regulatory T cells in cancer. Dr. Ager's research, in collaboration with colleagues at Columbia University, discovered multiple novel targetable vulnerabilities of the tumor-infiltrating regulatory T cell (Treg) state.
These vulnerabilities include the transcription factor TRPS1 and the killer cell lectin-like receptor KLRG1+Helios- phenotype. Alongside collaborators within the Department of Immunology, Dr. Ager's research is interrogating mechanisms underlying these novel factors to inform design and translation of new therapeutic strategies that selectively disable human tumor-infiltrating Tregs.
Significance to patient care
Cancer immunotherapy has become a pillar of cancer care. However, long-term durable responses remain restricted to a minority of patients, particularly in prostate cancer where most patients are resistant.
Sensitizing these patients to immunotherapy, or selecting patients most likely to respond, requires a deeper fundamental understanding of how immune responses succeed or fail. Dr. Ager's research applies state-of-the-art single-cell profiling technologies to this end.
This technology generates actionable discoveries that fuel novel drug development, optimization of existing therapeutic regimens and designs of innovative clinical trials to benefit patients at Mayo Clinic and beyond.