The Eil lab focuses on identifying and over-coming novel mechanisms of tumor-induced immune evasion, with the goal of engineering novel immune therapies and improving existing ones.
T cells, a type of immune cell that emigrates out of the thymus, can recognize and kill cancer cells. While T cells infiltrate many cancers, and their abundance is associated with patient survival, their function is constrained with tumors – allowing immune evasion and cancer progression.Yet, T cell based therapies for cancer (checkpoint blockade and the adoptive transfer of tumor-specific T cells) have changed the field of oncology over the past 10 years, yielding dramatic clearance of widespread cancer in some cases.
However, these successes are the exception with treatment failure remaining the rule, owing to tumor induced immune suppression and attendant T cell dysfunction. The tissue characteristics specific to tumors that drive the strong predisposition to immune evasion remain unclear. There remains a critical need to augment T cell antitumor function within cancers. While this topic remains an area of intense investigation, many have focused on cytokines (TGFβ), co-inhibitory signals (CTLA-4, PDL-1), and cell-cell interactions (regulatory T cells & myeloid derived suppressor cells) as mechanisms of tumor induced immune suppression. However, tissue and biochemical characteristics specific to tumors may also be important for T cell function.
A high abundance of cell death characterizes many tumors and is associated with poor prognosis. Our prior work demonstrated that cancer cell death results in the release of the potassium ion (K+; normally sequestered within the cell), into the surrounding tumor milieu thereby increasing the extracellular potassium ([K+]e). We found that ↑[K+]e directly suppresses T cell receptor (TCR) induced activation and drives metabolic reprogramming to maintain T cell stemness (Eil R et al., Nature, 2016 & Science, 2019). This prior work was the first demonstration that extracellular K+ is a major determinant of T cell cytokine production and maturation.
We use genetic engineering strategies with viral and non-viral (CRISPR-Cas9) techniques, multi-platform imaging, in vitro functional immune readouts, next-generation sequencing, and murine models of cancer to study T cell ion transport, activation and function within tumors. We apply these findings to develop new cancer immunotherapies and improve existing ones, with an emphasis on those involving the liver. As a surgeon-scientist, Dr. Eil has a unique perspective and platform, allowing us to extend our studies to clinical and research specimens as well as prospective clinical trials focusing on immunomodulation in patients with cancers involving the liver, bile ducts, and pancreas.
Work in the Eil Lab is generously supported by
- OHSU School of Medicine
- American Association for Cancer Research
- American Society of Clinical Oncology
- Pancreatic Cancer Action Network
- National Cancer Institute/ NIH