Published online Apr 15, 2024. doi: 10.4251/wjgo.v16.i4.1134
Peer-review started: December 29, 2023
First decision: January 20, 2024
Revised: January 26, 2024
Accepted: March 4, 2024
Article in press: March 4, 2024
Published online: April 15, 2024
Processing time: 103 Days and 5.3 Hours
Pancreatic cancer (PC) is characterized by its extremely aggressive nature and ranks 14th in the number of new cancer cases worldwide. However, due to its complexity, it ranks 7th in the list of the most lethal cancers worldwide. The pathogenesis of PC involves several complex processes, including familial genetic factors associated with risk factors such as obesity, diabetes mellitus, chronic pancreatitis, and smoking. Mutations in genes such as KRAS, TP53, and SMAD4 are linked to the appearance of malignant cells that generate pancreatic lesions and, consequently, cancer. In this context, some therapies are used for PC, one of which is immunotherapy, which is extremely promising in various other types of cancer but has shown little response in the treatment of PC due to various resistance mechanisms that contribute to a drop in immunotherapy efficiency. It is therefore clear that the tumor microenvironment (TME) has a huge impact on the resistance process, since cellular and non-cellular elements create an immunosuppressive environment, characterized by a dense desmoplastic stroma with cancer-associated fibroblasts, pancreatic stellate cells, extracellular matrix, and immuno
Core Tip: This study aims to analyze the main mechanisms of resistance to pancreatic cancer immunotherapy and the respective methods of manipulating these processes. Thus, this review provides a compilation of the main mechanisms of resistance to immunotherapy linked to the tumor microenvironment, genetic factors and those linked to T-cell immunosuppression. Finally, this study provides an insight into new avenues that can be followed to manipulate the factors linked to resistance, providing a more efficient treatment and a reduction in lethality.