Peter Xie

All Publications

• NFAT mediates pro-tumorigenic inflammation in cancer-associated fibroblasts in pancreatic ductal adenocarcinoma. Cell reports Guo, C., Griffin, M. F., Morgan, A. G., Foster, D. S., Parker, J. B., Januszyk, M., Lindsay, H. G., Guardino, N. J., Reveron-Thornton, R., Xie, P. Y., Valencia, C., Kuhnert, M. M., Korah, M., Gonçalves, A., Guo, J. L., Delitto, A. E., Agolia, J. P., Tabora, A. D., Dua, M. M., Visser, B. C., Poultsides, G. A., Delitto, D., Longaker, M. T., Norton, J. A. 2026; 45 (1): 116849

  Abstract

  Pancreatic ductal adenocarcinoma (PDAC) is characterized by a dense stroma, low immunogenicity, and resistance to therapy. Cancer-associated fibroblasts (CAFs) are key stromal cells within the tumor microenvironment (TME) that drive tumor progression. Interleukin-1 (IL-1) promotes fibrosis, pathogenic inflammation, and poor prognosis in PDAC. Using a single-cell multi-omic approach, we investigate the IL-1 signaling axis in human and mouse models of PDAC, identifying nuclear factor of activated T cells (NFAT) transcription factors as key mediators. IL1R1+ CAFs activate an inflammatory phenotype associated with elevated NFAT motif activity and gene expression. In vivo, NFAT inhibition in a mouse model of PDAC significantly reduces tumor weight and fibrosis, supporting its pro-tumorigenic role. Our findings suggest that NFAT mediates IL-1-induced inflammation in PDAC, highlighting its potential as a therapeutic target. This study demonstrates the power of multi-omic analyses to uncover therapeutic targets within the complex TME.

  View details for DOI 10.1016/j.celrep.2025.116849

  View details for PubMedID 41533513

• Protocol for orthotopic implantation of a collagen hydrogel to model pancreatic ductal adenocarcinoma in mice. STAR protocols Agolia, J. P., Xie, P. Y., Korah, M., Fallah, M., Reveron-Thornton, R. F., Guo, C., Reddy, B., Sivasubramanian, R., Longaker, M. T., Chaudhuri, O., Foster, D. S., Delitto, D. 2026; 7 (1): 104337

  Abstract

  Available mouse models for pancreatic ductal adenocarcinoma (PDAC) are limited by slow tumor development and failure to recapitulate key stromal and immune characteristics. Here, we present a protocol for generating a collagen hydrogel mouse model for orthotopic PDAC. We describe steps for embedding mouse pancreatic cancer cells in a dense collagen hydrogel and surgically implanting it into the mouse pancreas. Mouse PDAC tumors typically reach 1 cm in diameter by 10 days after implantation and show immune and stromal cell recruitment. For complete details on the use and execution of this protocol, please refer to Korah et al.1.

  View details for DOI 10.1016/j.xpro.2025.104337

  View details for PubMedID 41533505

• T Cells Tear Apart Confining Extracellular Matrix Via a Breaststroke-like Motion to Generate Migration Paths. bioRxiv : the preprint server for biology Ha, B., Xie, P., Johns, B., Allan, C., Korah, M., Delitto, D., Bollyky, P., Torok, N., Chaudhuri, O. 2025

  Abstract

  T cells migrate through soft tissues to target infected and abnormal cells and regulate immunity. T cell migration is typically studied in microfluidic devices or other contexts where there is a pre-existing migration path; how they create paths in confining nanoporous extracellular matrices (ECM), such as can occur during fibrosis and around tumors, remains unclear. Here, we studied T cell migration in confining collagen-rich matrices with a range of stiffness, viscoelasticity, mechanical plasticity, and shear strength, or the stress at which the material fails. Strikingly, only shear strength, the stress at which a material fails, not stiffness or viscoelasticity, correlates with migration. During migration, T-cells extend thin actin-rich, finger-like protrusions into the ECM, which then undergo a divergent breaststroke-like motion. Thus, T cells tear apart confining matrices using a breaststroke-like motion to generate migration paths.

  View details for DOI 10.1101/2025.10.03.680352

  View details for PubMedID 41256507

  View details for PubMedCentralID PMC12622025

• Disruption of fibroblast MYD88 signaling promotes antitumor immunity in pancreatic ductal adenocarcinoma. Cell reports Korah, M., Reveron-Thornton, R. F., Fallah, M., Xie, P. Y., Gonçalves, A., Guo, C., Agolia, J. P., Delitto, A. E., Flojo, R. A., Reddy, B., Yip, K. A., Lu, J. M., Tomasso, A., Tabora, A. D., Guo, J. L., Bauer-Rowe, K. E., Pham, B., Goyal, L., Kirane, A. R., Charville, G. W., Chaudhuri, O., Dua, M. M., Visser, B. C., Lee, B., Poultsides, G. A., Wan, D. C., Norton, J. A., Foster, D. S., Longaker, M. T., Delitto, D. 2025; 44 (10): 116347

  Abstract

  Pancreatic ductal adenocarcinoma (PDAC) continues to carry a dismal prognosis. The disease is characterized by a uniquely dense fibrotic matrix generated by cancer-associated fibroblasts (CAFs). We have previously demonstrated that fibroblast-driven chronic inflammation suppresses T cell function through a myeloid differentiation primary response protein 88 (MYD88)-dependent mechanism. While extensively studied in myeloid cells, the role of MYD88 signaling in CAFs and its effects on PDAC remain poorly understood. In this study, we identify a MYD88-driven inflammatory CAF population in PDAC using a combination of bulk, single-cell, and spatial transcriptomic studies. Using an innovative collagen gel implantation model, we demonstrate that loss of MYD88 in CAFs enhances T cell infiltration and suppresses tumor growth. Combining MYD88 inhibition with immune checkpoint blockade significantly reduces tumor size and enhances antitumor immune responses, underscoring its potential as a therapeutic target in PDAC.

  View details for DOI 10.1016/j.celrep.2025.116347

  View details for PubMedID 41004339