Samuel A. Rose, PhD, CRI Immuno-Informatics Fellow Memorial Sloan Kettering Cancer Center Area of Research: All Cancers, Brain Cancer Dr. Samuel A. Rose is examining the mechanisms through which regulatory T cells (Tregs) suppress immune responses via the cytokine IFNɣ. The effects of cytokines, which are secreted signaling proteins that coordinate immune response, depend on the identity of the cell receiving the cytokine’s signal—its type, location, and cytokine milieu. IFNɣ is a particularly important cytokine that drives many immune responses: it generally induces inflammation in response to diseased cells and its dysfunction is implicated in autoimmune disorders. Paradoxically, IFNɣ can also suppress immune responses in some contexts, including cancer and multiple sclerosis. Despite being critical for immunity, the contextual regulation of IFNɣ’s function remains poorly understood. Here, Dr. Rose is investigating how Tregs provide a context that directs IFNɣ to be anti-inflammatory. Thus far, he has observed that mice with multiple sclerosis experience worse inflammation when their Treg cells cannot produce IFNɣ. Interestingly, this effect is specific to female mice, whereby IFNɣ appears to tame the generally more active female immune system. By studying this phenomenon using technologies that capture the expression of genes and their regulation in thousands of individual cells in mice, Dr. Rose aims to provide a high-resolution picture of how cell populations respond to cytokines. Current analytical methods cannot assess how cells respond to multiple concurrent signals, so he is testing computational approaches for modeling the combined effect of cytokines in cells to ultimately determine how IFNɣ activity is changed by additional signals. Through searching for similar gene activity in human cancer datasets, including samples from patients with glioblastoma, he hopes to determine whether cancer cells use IFNɣ to suppress immune response and evade immunity, and how we might be able to counteract. Projects and Grants Learning contextual determinants of interferon-gamma signaling during immunity Memorial Sloan Kettering Cancer Center | Brain Cancer, All Cancers | 2023 | Dana Pe’er, PhD
