Leukocytes recruited to and persistent within chronically inflamed tissues play critical roles in fostering neoplastic progression. Immunotherapies designed to reprogram protumoral immune microenvironments have gained clinical traction in many solid tumors, but pancreatic ductal adenocarcinoma (PDAC) has thus far failed to respond to single-agent immunotherapy. Recent preclinical studies have indicated that combinatorial immunotherapy may yield improved response rates in PDAC, especially combinations intended to both reprogram immunosuppressive myeloid cells and antagonize T cell inhibitory pathways. However, the immune microenvironment of human PDAC is heterogeneous and has not been extensively characterized in situ. As such, functionally significant immune biomarkers are urgently needed to better stratify patients for appropriate immunotherapeutic combinations.