Insights from preclinical models have fueled the rapid development and remarkable clinical success of new therapies designed to unleash the immune system to recognize and eliminate advanced malignancy. Where highly toxic and non-specific chemotherapeutics have failed, the unprecedented success of cancer immunotherapies is creating new hope for cancer patients. However, not all patients respond to current treatments. Some types of cancer, such as pancreatic cancer, are uniquely resistant to even the most aggressive therapies. Thus, the lab's goal is to uncover why the immune system fails to eradicate such deadly malignancies in order to develop safe and durable immune-based treatments for cancer patients. We use many technologies and approaches including gene editing of primary T cells with CRISPR/Cas9, cloning and expression and functional analyses of novel T cell receptors, adoptive cell therapy with genetically modified T cells and immune checkpoint blockade. T cells that recognize and respond to cancer are tracked in vivo using flow cytometry, multiparameter immunofluorescence, 2-photon intravital imaging and by single cell gene expression analysis.
Bioinformatic analysis of tumor-infiltrating CD4 T cells in a large human pancreatic cancer dataset. Read more here.
2-photon imaging of pancreas tumor (red), genetically engineered T cells (green), extracellular matrix (blue) and cross-presenting dendritic cells (yellow). By Meagan Rollins.
Immunofluorescence staining of resected PDA patient tumor showing tumor cytokeratin-19 (green) and MHC-I (red) on cells (blue nuclei) in the tumor microenvironment.
Detection of tumor (neoantigen)-specific T cells in pancreatic cancer using fluorescently labeled MHC class I tetramers. Tetramer generation and staining by Adam Burrack.
Schematic of T cell receptor exchange (TRex) mouse strain generation. Leveraging cargo delivery by AAV and CRISPR Cas9-directed homology repair, our lab developed a fast and reliable method of generating TCR transgenic mice. Read more here.
High-resolution ultrasound of a pancreatic tumor mass in control (top row) or following immunotherapy (bottom row). By Adam Burrack.
Dr. Meagan Rollin's imaging on the cover of JCI Insight Volume 7, Issue 7. 2-photon microscopy of type 1 dendritic cells infiltrating pancreatic cancer.
Pancreatic tumor cells (purple), CD8+ T cells (red), macrophages (pink) and the immune checkpoint molecules PD-1 (yellow) and PD-L1 (green) expression in human pancreatic cancer. These data suggest that some pancreatic cancers may contain tumor-specific T cells.
Cover of Cancer Immunology Research.