Stromal Factors

  • Tumor stroma comprises of various cells such as fibroblasts, endothelial cells, immune cells, adipocytes. Stromal cells have emerged as potential drivers in immune modulation through the release of cytokines, chemokines and other soluble factors and their expression of ligands for inhibitory receptors such as CTLA-4 and PD-1. T cell infiltration to the tumor could be physically impeded by high tumor stromal density and by the formation of compact barrier structures. During tumor progression, the degradation and remodeling of matric components is a continuous dynamic process. In cancer tissues, fibroblasts differentiate into associated fibroblasts expressing activation markers, such as alpha-smooth muscle actin (αSMA), stromal cell-derived factor-1α (SDF-1α), fibroblast activation protein (FAP). Cancer Associated Fibroblasts (CAFs) favor tumor progression via collagen production. In addition, many fibroblasts at the tumor site release enzymes involved in matrix degradation such matrix metallo-proteinases (MMPs) and cross linking of collagen fibers as lisle oxidases (LOX).  Preliminary preclinical studies targeting stromal components or chemokines associated with CAFs could lead to enhanced T cell infiltration in combination with checkpoint therapies.

    Studies include:

    • Screen for stromal factors that impede lymphocyte infiltration in response to drug candidate

    • Discover tumor stromal targets that can enhance lymphocyte infiltration.

    • Combination studies of stromal targeting agents and lymphocytes.