Immunotherapy, the use of agents that stimulate or suppress immune responses to combat disease, has revolutionized the treatment of certain types of cancer. However, many cancers are unresponsive to immunotherapy for reasons that remain poorly understood. Immune cells cannot execute their function in isolation, but require interactions with other immune and non-immune cells. In a large collaborative systems biology effort, we discovered multiple cellular communities—or “hubs” where malignant and immune cells interact in the tumors of patients with colorectal cancer. Furthermore, we found that tumors that were likely to respond to immunotherapy contained different types of hubs than those who don’t respond. By pursuing the characterization of immune hubs in solid tumors, we hope to identify molecular mechanisms that could be harnessed to design novel immunotherapies for currently non-responsive tumors.