Role of immune cells in pancreatic cancer from bench to clinical application: An updated review

BACKGROUND: Pancreatic cancer (PC) remains difficult to treat, despite the recent advances in various anticancer therapies. Immuno-inflammatory response is considered to be a major risk factor for the development of PC in addition to a combination of genetic background and environmental factors. Although patients with PC exhibit evidence of systemic immune dysfunction, the PC microenvironment is replete with immune cells. METHODS: We searched PubMed for all relevant English language articles published up to March 2016. They included clinical trials, experimental studies, observational studies, and reviews. Trials enrolled at Clinical trial.gov were also searched. RESULTS: PC induces an immunosuppressive microenvironment, and intratumoral activation of immunity in PC is attenuated by inhibitory signals that limit immune effector function. Multiple types of immune responses can promote an immunosuppressive microenvironment; key regulators of the host tumor immune response are dendritic cells, natural killer cells, macrophages, myeloid derived suppressor cells, and T cells. The function of these immune cells in PC is also influenced by chemotherapeutic agents and the components in tumor microenvironment such as pancreatic stellate cells. Immunotherapy of PC employs monoclonal antibodies/effector cells generated in vitro or vaccination to stimulate antitumor response. Immune therapy in PC has failed to improve overall survival; however, combination therapies comprising immune checkpoint inhibitors and vaccines have been attempted to increase the response. CONCLUSION: A number of studies have begun to elucidate the roles of immune cell subtypes and their capacity to function or dysfunction in the tumor microenvironment of PC. It will not be long before immune therapy for PC becomes a clinical reality.