The Translational Tumor Immunology Lab, led by Alfred E. Chang, MD and Qiao Li, PhD, has been working in the area of tumor immunology and cancer immunotherapy for more than 20 years. Our research is leading us to develop new strategies to induce immune cells to fight cancer. We perform preclinical studies in animal models and conduct clinical trials in patients in close collaboration with the U-M Rogel Cancer Center. Our goal is to identify novel directions in cancer immunotherapy, so that we may improve efficacy and broaden the patient populations that can benefit.
Current Research in the Translational Tumor Immunology Lab
Background
For many years, T cells were believed to be the primary immune cell involved in anticancer immunity. While the role of T cells is indeed crucial, T cell-based immunotherapies have not been as effective as scientists had hoped, and new strategies are needed.
In addition, a small population of tumor cells — typically between about 5% and 10%— known as cancer stem cells (CSCs) have been shown to be responsible for cancer relapse and metastasis. These cells resist conventional anticancer treatments, including radiation, chemotherapy as well as immunotherapy, and without effectively targeting them, cancer is likely to recur and spread.
Our Approach
Our current work builds on our early research on T cells, including generating, activating and expanding tumor-reactive T cells for adoptive immunotherapy using a number of strategies and signaling pathways.
Our research has extended to also focus on the role of B cells in cancer immunity. Our investigations indicate that B cells, key players in humoral immunity and antibody production, have been an under-recognized factor in the immune response to cancer. We found that combining B-cell and T-cell based strategies can amplify the anti-tumor immune response.
Another new direction in cancer immunology pursued in our laboratory is development of a novel vaccine based on, and specifically targeting, cancer stem cells. In this approach, we are using protein biomarkers to identify CSCs so they can be presented to immune cells to activate anti-CSC immunity.
Contributions to Science
Our investigators’ work over the years has led to a number of scientific contributions as we develop and translate new approaches to cancer immunity from the laboratory into clinical trials.
Our work with T cells led to develop methods for activating these cells in vitro and augmenting their antitumor activity using monoclonal antibodies and cytokines. Our T-cell work also led us to identify and characterize subsets of tumor-specific T-cell populations. This work led to clinical trials of activated T cells to treat melanoma and renal cell carcinoma patients at the U-M Rogel Cancer Center.
While another immune cell type, B cells, had been known for many years to be involved in infectious disease immunity, we were the first to demonstrate their unique functionalities in antitumor immunity. We identified multiple underlying mechanisms, and also showed that combining B- and T-cell immune therapy approaches led to a stronger anti-tumor response than either approach on its own, highlighting the promise of combined, synergistic cell therapies.
In addition, our team developed and demonstrated in animal models a cancer stem cell (CSC) vaccine to specifically target these resistant cells that lead to cancer metastasis and recurrence. As part of this research, we found new ways to isolate CSCs and combine CSC-based vaccines with immune checkpoint inhibitors to activate more potent anti-tumor immunity.
