Jeremy B. Jacox, MD, PhD

Overview

Aim: Tumor Biology

Immunotherapy, treatments that stimulate the body’s immune system to fight cancer, has been transformational for some types of cancer, but largely ineffective for pancreatic cancer. This lack of efficacy can be attributed, in part, to the highly immunosuppressive tumor microenvironment that pancreatic tumor cells reside in. One key feature of pancreatic tumors that contributes to the immunosuppressive microenvironment is the dense tissue that surrounds them called stroma. Stroma limits the ability of immune cells, specifically CD8+ T cells, to travel to and enter the tumor microenvironment. The lack of stroma in pre-clinical models of pancreatic cancer is one limiting factor in designing and evaluating immunotherapies that will allow CD8+ T cells to access the tumor microenvironment. Additionally, many preclinical PDAC models also lack the mutant protein tags expressed on tumor cells, called neoantigens. Neoantigens allow the immune system to recognize tumors and are responsible for the activation of T cells to mount an anti-tumor immune response. These two limitations are potential barriers to developing durable immunotherapies that could be effective for pancreatic cancer patients.

Hirshberg Foundation 2026 Seed Grant recipient, Jeremy Jacox, MD, PhD, an Instructor of Medicine at Yale University, and his collaborators have generated a new organoid-derived preclinical model, called NINJA PDAC, that more closely resembles the tumor microenvironment and stromal interactions found in patients. Preliminary data from this model has suggested the CXCR4/CXCL12 signaling pathway as a potential mediator of CD8+ T cell exclusion from the tumor microenvironment. Dr. Jacox’s project Synergistic bypass of barriers to neoantigen-driven immunity in pancreatic cancer aims to identify mechanisms that regulate the exclusion of CD8+ T cells from the PDAC tumor microenvironment. Using the NINJA PDAC model, Dr. Jacox will identify and preclinically evaluate novel combination therapies to convert immune cell excluded tumor microenvironments to T cell infiltrated ones that allow for effective immunotherapy interventions.

The Hirshberg Foundation is proud to support Dr. Jacox’s research with a 2026 Hirshberg Foundation Seed Grant Award. His work to uncover ways to increase T cell infiltration into stromal-rich PDAC tumors could allow the promise of immunotherapy to become a reality for pancreatic cancer patients.

Dr. Jacox wrote to say, “Thank you for this wonderful news! It is a great honor to be able to accept this 2026 Seed Grant award among many potential deserving applicants. I am deeply grateful for your trust and will pursue this work enhancing immunotherapeutics in pancreatic cancer, in memory of all those who have been affected by pancreatic diseases. I look forward to working with the Hirshberg Foundation and its esteemed community in the upcoming year and beyond.”