The Spatial Distribution of Immune Cells in Tumors

The goal of immunotherapy is to mobilize the immune system to kill cancer cells. Immunotherapy is more effective and, in general, the prognosis is better, when more immune cells infiltrate the tumor. We explore the question of whether the spatial distribution rather than just the density of immune cells in the tumor is important in forecasting whether cancer recurs. To do this, we have developed statistical techniques (occupancy, fractal dimension difference and a maximum entropy application) to quantify the spatial distribution of discrete point-like objects. For example, to compute occupancy, a grid of squares is placed over image. Squares are assigned 1’s (0’s) corresponding to yes (no) answers to a binary question asked of each square, e.g., “Is there at least one B cell in the square?” Occupancy is the fraction of squares with 1’s. We apply these techniques to tumor-infiltrating lymphocytes (TILs) in human triple negative breast cancer. Our results indicate that B and T cells in good outcome tumors (no recurrence within 5 years) are spatially dispersed, while B cells in poor outcome tumors (recurrence within 3 years) are more confined. Our results highlight the importance of spatial distribution of immune cells within tumors with regard to clinical outcome, and raise new questions on their role in cancer recurrence.