Beyond density: Spatial distribution of lymphocytes in triple-negative breast cancer tumors

The goal of immunotherapy is to mobilize the immune system to kill cancer cells. For solid tumors, immunotherapy is more effective if there is a high density of immune cells in the tumor. In fact, even without immunotherapy, the prognosis is better if a high density of immune cells known as lymphocytes are in the tumor. Lymphocytes consist of T and B cells. Killer T cells can destroy cancer cells and infected cells. B cells are best known for making antibodies. We consider triple negative breast cancer (TNBC) which is a particularly aggressive form of breast cancer. While the density of tumor-infiltrating T cells is now widely accepted to predict TNBC outcomes, the clinical significance of intratumoral B cell density is less clear. We have developed a number of techniques to quantify the spatial distribution of tumor-infiltrating T and B cells in TNBC, including box-counting, fractal dimension, and maximum-entropy methods. These methods allow us to measure the clustering or dispersion of lymphocytes on a wide range of spatial scales while being able to control for differences in overall density. Our results indicate that B cells in good-outcome tumors are more spatially dispersed, while B cells in poor-outcome tumors are more confined, independent of their average density.