Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer, and its micrometastases are commonly seen in clinical practice. Although great progress has been made in immunotherapy for malignancies in recent years, immune checkpoint blockade focusing on programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) has changed the clinical diagnosis and treatment of non-small cell lung cancer, melanoma, urothelial carcinoma, and renal carcinoma. However, the clinical effect of immunotherapy in PDAC is limited by the low immunogenicity and unique tumor microenvironment (TME) of PDAC. With the research advances in PDAC-TME, an in-depth analysis of the highly complex interaction network between immune system, tumor cell, and matrix signal may help to develop a rational combination of immunotherapies for PDAC. By elaborating on the unique immunological features of PDAC-TME, this article reviews the potential treatment opportunities for PDAC and the advances in clinical research.