학술논문

Immunotherapy in Pancreatic Cancer: Why Do We Keep Failing? A Focus on Tumor Immune Microenvironment, Predictive Biomarkers and Treatment Outcomes.
Document Type
Article
Source
Cancers. May2022, Vol. 14 Issue 10, p2429-N.PAG. 14p.
Subject
*PANCREATIC tumors
*TREATMENT effectiveness
*TUMOR markers
*IMMUNOTHERAPY
Language
ISSN
2072-6694
Abstract
Simple Summary: In pancreatic cancer, immunotherapy and targeted therapies have not brought about the therapeutic revolution that has been observed in other malignancies. Among the reasons to explain this difference is the possibly crucial role played by the pancreatic tumor microenvironment, which has unique features and is different from that of other neoplasms. The aim of this review is to provide a comprehensive overview of the distinctive tumor immune microenvironment of pancreatic cancer and to summarize existing data about the use of immunotherapy and immune biomarkers in this cancer. The advent of immunotherapy and targeted therapies has dramatically changed the outcomes of patients affected by many malignancies. Pancreatic cancer (PC) remains one the few tumors that is not treated with new generation therapies, as chemotherapy still represents the only effective therapeutic strategy in advanced-stage disease. Agents aiming to reactivate the host immune system against cancer cells, such as those targeting immune checkpoints, failed to demonstrate significant activity, despite the success of these treatments in other tumors. In many cases, the proportion of patients who derived benefits in early-phase trials was too small and unpredictable to justify larger studies. The population of PC patients with high microsatellite instability/mismatch repair deficiency is currently the only population that may benefit from immunotherapy; nevertheless, the prevalence of these alterations is too low to determine a real change in the treatment scenario of this tumor. The reasons for the unsuccess of immunotherapy may lie in the extremely peculiar tumor microenvironment, including distinctive immune composition and cross talk between different cells. These unique features may also explain why the biomarkers commonly used to predict immunotherapy efficacy in other tumors seem to be useless in PC. In the current paper, we provide a comprehensive and up-to-date review of immunotherapy in PC, from the analysis of the tumor immune microenvironment to immune biomarkers and treatment outcomes, with the aim to highlight that simply transferring the knowledge acquired on immunotherapy in other tumors might not be a successful strategy in patients affected by PC. [ABSTRACT FROM AUTHOR]