Pancreatic cancer has the lowest 5-year survival rate of all cancers, and pancreatic ductal adenocarcinoma (PDAC) is the most common subtype. Immune checkpoint inhibitors (ICIs) that improve immune cells’ ability to kill tumor cells are useful for other cancers. but single ICIs don’t work well for PDAC, possibly because the PDAC tumor microenvironment inhibits immune activity. Some research suggests that the efficacy of ICIs can be improved by combining the ICIs with other treatments, such as chemotherapy, multiple antibodies, and drugs targeting specific components of the tumor microenvironment. Several cell types and their interactions can potentially be targeted. such as those of regulatory T cells (Tregs), tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), and pancreatic stellate cells (PSCs). In addition, continued research on the diverse mechanisms of the immune checkpoint molecules and their receptors could reveal new strategies for treatment. Future work should focus on optimizing immune cell numbers/activity in the microenvironment, identifying effective biomarkers, and developing individualized treatments to improve the prognosis of this devastating disease.