The accumulation of desmoplastic stroma, infiltration of immunosuppressive cells including myeloid derived suppressor cells (MDSCs), tumor associated macrophages (TAMs), cancer‐associated fibroblasts (CAFs), and regulatory T cells (Tregs), as well as tumor associated cytokine such as TGF-β, IL-10, IL-35, CCL5 and CXCL12 construct an immunosuppressive microenvironment of pancreatic cancer, which presents challenges for immunotherapy. This evidence concerns the gene CXCL12 and familial pancreatic carcinoma.