Yale Cancer Center Researchers Awarded $2.8 Million Cancer Systems Immunology Grant

Marcus Bosenberg, MD, PhD

Yale Cancer Center (YCC) researchers were awarded a $2.8 million grant from the National Cancer Institute to evaluate and model cytokine signaling related to immunotherapy for cancer. Cytokines are powerful hormone-like molecules of the immune system that are utilized by a variety of different cell types within tumors to communicate with one another and to send signals to sites outside of the tumor. The scientists and their laboratories will collaborate to determine how cells within the tumor microenvironment utilize cytokine signaling and will generate computational models to explain this behavior.

Kathryn Miller-Jensen, PhD, Associate Professor of Biomedical Engineering and Molecular, Cellular, and Developmental Biology, along with Marcus Bosenberg, MD, PhD, Interim Director of the Yale Center for Immuno-Oncology (YCIO) and Professor of Dermatology, Pathology, and Immunobiology, will lead the research. “This grant reflects the type of multidisciplinary research that we encourage in the YCIO, combining a broad range of required skills from several laboratories,” said Bosenberg.

The research team also includes Harriet Kluger, MD, Professor of Medicine (Medical Oncology) and Co-Director of the Yale SPORE in Skin Cancer, and Susan Kaech, PhD, Professor and Director of the NOMIS Center for Immunobiology and Microbial Pathogenesis at the Salk Institute for Biological Studies.

In addition to research funding, the award will establish Miller-Jensen and Bosenberg as members of the Cancer Systems Biology Consortium (CSBC), a science network founded by the National Cancer Institute (NCI) devoted to enhancing the role of systems biology approaches to cancer research.

The work will take advantage of recent advances that enable measurements of gene expression and cytokine levels in individual cells in tumors. Using computational algorithms, the team will construct networks of cytokine communication between immune cells in melanoma tumors. By tracking how these networks change in tumors that are responsive or unresponsive to immunotherapy, novel targets will be identified and evaluated further. “High-throughput single-cell data sets are information-rich but very complex. Systems biology approaches are ideally suited to reveal the underlying biology that can be translated to the clinic,” said Miller-Jensen.

The work of Miller-Jensen and Bosenberg was enabled by pilot funding from an NCI U54 Cancer Systems Biology grant directed by Andre Levchenko, PhD, John C. Malone Professor of Biomedical Engineering and Director, Systems Biology Institute at Yale West Campus.