• Motoki Miyazawa, Masahiro Katsuda, Manabu Kawai, Seiko Hirono, Ken-Ichi Okada, Yuji Kitahata, and Hiroki Yamaue.
• Second Department of Surgery, School of Medicine, Wakayama Medical University, Wakayama, Japan.
• J Hepatobiliary Pancreat Sci. 2021 May 1; 28 (5): 419-430.

AbstractAdvances in immunotherapy against advanced cancers can be considered stunning and epoch-making. Meanwhile, efficacy of immune-based therapies, especially immune checkpoint inhibitors, remains insufficient in pancreatic ductal adenocarcinoma, differing from other immunogenic cancers. To date, neither immunotherapies targeting immune system acceleration nor release of immunologic brakes have been able to overcome the robust immune barrier in the pancreatic tumor microenvironment, which is characterized by rich fibrotic stroma and accumulation of immunosuppressive myeloid cells. However, by receiving an immune checkpoint blockade, patients with abundant tumor-infiltrating lymphocytes in pancreatic ductal adenocarcinoma clearly have better prognosis, and patients with mismatch repair deficiency have achieved better outcomes, albeit in a small population of pancreatic ductal adenocarcinoma. We overview recent preclinical and clinical studies that have been concerned with immune-based therapies including cancer vaccine and immune checkpoint inhibitors. By providing a deep insight into the immunosuppressive tumor microenvironment, we suggest the possibility of comprehensive immune intensification that could reverse the tumor microenvironment, making it conducive to cytotoxic T lymphocyte activity for overcoming pancreatic ductal adenocarcinoma.© 2021 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

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