| Pancreatic ductal adenocarcinoma has a poor 5-year survival rate that makes it one of the most fatal human malignancies. Unfortunately, despite the serious improvement in the survival of most cancers, there has been a minor advance in pancreatic cancer (PC). Major advances in PC treatment have been assessed over the bygone twenty-year time span, yet some complications make the survival of the patients shorter. Getting to know the PC tumor microenvironment (TME) and the immunosuppression that happens during the pathogenesis of this malignancy could be a great help to understand the nature of the immune system and find better treatment modalities based on it. Although many immune cells are present in PC, immunosuppression of the TME leads to severe immune dysfunction in the patients, therefore immune effectors fail to do their functions. Lately, immunotherapy has been presented as one of the promising treatment strategies for different malignancies including hepatocellular carcinoma, melanoma, non-small cell lung cancer, and kidney cancer. In PC, there has been shown promising results centered around the TME, immune checkpoint inhibitors, cancer vaccines, and other approaches especially when used as combinational therapy. Here we dig a little deeper into the role of the immune system and possible therapeutic options in the treatment of PC. |