Cho Lab

Advances in immunotherapy over the past decade have dramatically changed the treatment and prognosis of some types of cancer. Many patients with once untreatable, advanced disease now have the real possibility of a cure through therapies that successfully turn the body's immune system against cancer cells. But while immunotherapy can be remarkably effective for some patients against certain types of cancers, its promise hasn't extended to all types. Many, including pancreatic and hepatobiliary cancers, remain intrinsically invisible to the human immune system.

Since 2006, the Cho Lab, led by Dr. Clifford S. Cho, has worked to understand — and overcome — the mechanisms by which cancer cells circumvent the immune system and to develop new ways to broaden and strengthen cancer immunotherapy. We do this by conducting pre-clinical research to identify new and combinatory immunotherapy methods that can be translated to clinical practice. Our goal is to improve immunotherapy for all of our patients with all types of cancers, including those that have, to date, proven resistant to immune-based therapies.

Developing cancers deploy many mechanisms to evade and suppress the immune system. Recent immunotherapy breakthroughs overcome some of these mechanisms, but new methods are still needed to improve effectiveness. Gaining new insights and developing new approaches have been the focal point of our research efforts for well over a decade.

Our lab focuses on ways to expand and strengthen immunotherapy by investigating the physiology of CD8+ memory T cells — an important family of immune cells that form the basis of immunity — and learning how best to integrate these fascinating, long-lived cells into existing and new immune-based therapies. Much of our work centers on how to scale these new methods for use with patients.  We have also seen that this subset of immune cells is especially effective at eradicating cancer stem cells – a property that may have major implications for cancer immunotherapy. In addition, we investigate the synergistic use of immunotherapies with other cancer treatments, such as radiation, chemotherapy, surgery and a novel ultrasound ablation technology developed at U-M, known as histotripsy.

Our efforts and discoveries have led to several scientific advances related to cancer immunotherapy: Our work has led to a greater understanding of how different types of cancers evade the immune system, including the discovery that CD8+ memory T cells are uniquely resistant to cancer immune suppression. Building upon that work, we have found that CD8+ memory T cells are especially well suited for a commonly used type of immunotherapy, known as adoptive cell transfer. Further, we've overcome one of the greatest challenges to using CD8+ memory T cells in immunotherapy — their very small populations — and developed methods to isolate and expand them in large quantities so that they might then be infused into patients with cancer.

We discovered that histotripsy, a novel method of noninvasive tumor ablation developed at U-M, stimulates a surprisingly profound immune response to tumors. The ability to promote a strong immune response holds great promise for working synergistically, and very effectively, with immunotherapy. We also are elucidating the complex interplay between immunotherapy and cancer stem cells (CSCs), which drive disease progression, and uncovering new ways to inhibit them.