Our Research Vision

How is T cell lineage controlled in the tumor microenvironment? A specific type of T cell, regulatory T cells (Tregs), work to suppress the cytotoxic effects of other T cell subsets, and are generally considered a poor prognostic indicator in many cancers. We recently discovered that these cells can be reprogrammed to become potent anti-tumor effector cells using a combination of immunomodulatory antibody treatments. Using high resolution multiplex imaging & single-cell RNA spatial transcriptomics, we discovered unique subcellular and spatial changes occurring in these and other antigen presenting cells in the tumor microenvironment. We now investigate how the pathways controlling these changes can be leveraged in the face of highly suppressive immunolandscapes. This work shed light on the plasticity of Tregs, but also the requirement for cellular neighborhoods of the correct composition to potentiate immune responses. We believe this has the potential to uncouple the accumulation of Tregs in the tumor microenvironment from poor prognostic outcome, and could instead be leveraged to improve patient outcomes.

How are immune responses potentiated or halted within the tumor microenvironment? Our studies have revealed that responsive and nonresponsive tumor microenvironments have distinct cellular spatial patterns. At both the protein and RNA level, we have found that micro-neighborhoods within these tumors exist and react to immunotherapies. The mechanisms dictating both the formation and maintenance of these changes/patterns remain unknown. We are now interrogating the timescale of these responses and perturbation of these neighborhoods with the goal of improving patient therapeutic approaches.

Can we use bacteria as programmed cell death inducers to induce potent antitumor responses? Both radiation and chemotherapy rely on two main factors to aid in immune cell-mediated responses: direct tumor cell death and the subsequent liberation of tumor antigens upon cell death. However, many cancers hijack cell death pathways to survive and propagate, and then secrete a variety of factors that can alter the cell death capability of host immune cells in the TME. Lytic cell death is highly immunogenic and has the potential to overcome these immunosuppressive strategies by recruiting immune cell swarms. In short, the way a cell dies matters. We aim to expand upon this concept and employ synchronized cell death within the tumor to decrease immunosuppressive myeloid subsets and tumor volume, while simultaneously invoking an influx of inflammatory immune cells.