The clinical terrain of immunotherapies in heterogeneous pancreatic cancer: unravelling challenges and opportunities

Pancreatic ductal adenocarcinoma (PDAC) is the most common and aggressive type of pancreatic cancer and has abysmal survival rates. In the past two decades, immunotherapeutic agents with success in other cancer types have gradually been trialled against PDACs at different stages of cancer progression, either as a monotherapy or in combination with chemotherapy. Unfortunately, to this day, chemotherapy still prolongs the survival rates the most and is prescribed in clinics despite the severe side effects in other cancer types. The low success rates of immunotherapy against PDAC have been attributed most frequently to its complex and multi-faceted tumour microenvironment (TME) and low mutational burden. In this review, we give a comprehensive overview of the immunotherapies tested in PDAC clinical trials thus far, their limitations, and potential explanations for their failure. We also discuss the existing classification of heterogenous PDACs into cancer, cancer-associated fibroblast, and immune subtypes and their potential opportunity in patient selection as a form of personalisation of PDAC immunotherapy. & COPY; 2023 The Pathological Society of Great Britain and Ireland.

Automated summary

Pancreatic ductal adenocarcinoma (PDAC) is a common and aggressive type of pancreatic cancer with low survival rates. Immunotherapeutic agents have been tested against PDACs, but chemotherapy remains the main treatment due to its higher success rates. The complex tumor microenvironment and low mutational burden are the main factors contributing to the low success of immunotherapy. This review provides an overview of the immunotherapies tested in PDAC clinical trials, their limitations, and discusses the potential for personalized PDAC immunotherapy based on the classification of heterogenous PDACs.