Pancreatic cancer, predicted to become the second leading cause of cancer death by 2015, eludes treatment for several reasons, not the least of which is tumor heterogeneity. For example, pancreatic tumors may run “hot” or “cold”—influencing how they respond to immunotherapy. Hot tumors are filled with T cells. Cold tumors have fewer T cells and are often considered to be less sensitive to immunotherapy. But how does a pancreatic tumor become hot or cold in the first place? And can a pancreatic tumor’s “temperature” be controlled to enhance immunotherapy? To answer these questions, scientists based at Penn Medicine's Abramson Cancer Center (ACC) probed tumor heterogeneity, the ways tumor cells manifest diversity with respect to movement, replication, metastasis, and treatment response. After experimenting with a library of pancreatic cancer cell clones by implanting them in immunocompetent mice, the scientists determined that tumor-cell-intrinsic factors shape the tumor immune microenvironment ...