Pancreatic ductal adenocarcinoma (PDAC) is considered immunologically “cold,” and treatment with immune checkpoint blockade targeting PD-1/PD-L1 is only effective in a subset of patients. Karamitopoulou et al. use an automated system, in addition to next-generation sequencing, to analyze the tumor microenvironment (TME) from patients with microsatellite-stable (MSS) and -instable (MSI) PDAC. Distinct patterns of PD-1/PD-L1 expression that correlate with different patient outcomes and characteristics of the TME, including immune composition and cell proximity, are identified. These data provide a deeper understanding of the PDAC TME and its heterogeneity and could aid in treatment decisions for patients with PDAC. Read more in this issue on page 1439. Original image from Fig. 4. Artwork by Lewis Long.