Pancreatic Cancer Immuno-oncology in the Era of Precision Medicine

Abstract

Pancreatic malignancies carry a dismal prognosis globally, with pancreatic adenocarcinomas (PDAC) being particularly aggressive and stubborn. Unfortunately, several therapeutic strategies that show promise in other cancers have failed to make sizeable impact on pancreatic tumor outcomes. Responses to immunotherapies are especially rare in pancreatic cancer, and patients are in need of innovative approaches that can result in more durable responses. Current research in preclinical models and humans has suggested this resistance is due to a uniquely inflammatory and dysfunctional tumor microenvironment; these findings lay the groundwork for targeting these barriers and improving outcomes. Clinical analyses have also revealed unprecedented heterogeneity in tumor and stromal biology of PDAC, underscoring the need for more personalized approaches and combinatorial therapies. This review will highlight the current state of translational research focusing on PDAC immunity, summarize ongoing clinical efforts to tackle PDAC vulnerabilities, and underscore some unresolved challenges in implementing therapies more broadly. A better understanding of immune contexture and tumor heterogeneity in this disease will greatly accelerate drug discovery and implementation of precision medicine for PDAC.

Keywords: Cancer; Immunotherapy; Oncology; Pancreatic cancer; Precision therapy; Targeted therapy.