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Locoregional Therapies and Remodeling of Tumor Microenvironment in Pancreatic Cancer.

ABSTRACT: Despite the advances made in treatment, the prognosis of pancreatic ductal adenocarcinoma (PDAC) remains dismal, even in the locoregional and locally advanced stages, with high relapse rates after surgery. PDAC exhibits a chemoresistant and immunosuppressive phenotype, and the tumor microenvironment (TME) surrounding cancer cells actively participates in creating a stromal barrier to chemotherapy and an immunosuppressive environment. Recently, there has been an increasing use of interventional radiology techniques for the treatment of PDAC, although they do not represent a standard of care and are not included in clinical guidelines. Local approaches such as radiation therapy, hyperthermia, microwave or radiofrequency ablation, irreversible electroporation and high-intensity focused ultrasound exert their action on the tumor tissue, altering the composition and structure of TME and potentially enhancing the action of chemotherapy. Moreover, their action can increase antigen release and presentation with T-cell activation and reduction tumor-induced immune suppression. This review summarizes the current evidence on locoregional therapies in PDAC and their effect on remodeling TME to make it more susceptible to the action of antitumor agents.

SUBMITTER: De Grandis MC

PROVIDER: S-EPMC10454061 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Locoregional Therapies and Remodeling of Tumor Microenvironment in Pancreatic Cancer.

De Grandis Maria Caterina MC Ascenti Velio V Lanza Carolina C Di Paolo Giacomo G Galassi Barbara B Ierardi Anna Maria AM Carrafiello Gianpaolo G Facciorusso Antonio A Ghidini Michele M

International journal of molecular sciences 20230811 16

Despite the advances made in treatment, the prognosis of pancreatic ductal adenocarcinoma (PDAC) remains dismal, even in the locoregional and locally advanced stages, with high relapse rates after surgery. PDAC exhibits a chemoresistant and immunosuppressive phenotype, and the tumor microenvironment (TME) surrounding cancer cells actively participates in creating a stromal barrier to chemotherapy and an immunosuppressive environment. Recently, there has been an increasing use of interventional r ...[more]

PMID: 37628865

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Project description:BackgroundAccumulating evidence suggests that anoikis plays a crucial role in the onset and progression of pancreatic cancer (PC) and pancreatic neuroendocrine tumors (PNETs); nevertheless, the prognostic value and molecular characteristics of anoikis in cancers are yet to be determined.Materials and methodsWe gathered and collated the multi-omics data of several human malignancies using the TCGA pan-cancer cohorts. We thoroughly investigated the genomics and transcriptomics features of anoikis in pan-cancer. We then categorized a total of 930 patients with PC and 226 patients with PNETs into distinct clusters based on the anoikis scores computed through single-sample gene set enrichment analysis. We then delved deeper into the variations in drug sensitivity and immunological microenvironment between the various clusters. We constructed and validated a prognostic model founded on anoikis-related genes (ARGs). Finally, we conducted PCR experiments to explore and verify the expression levels of the model genes.ResultsInitially, we identified 40 differentially expressed anoikis-related genes (DE-ARGs) between pancreatic cancer (PC) and adjacent normal tissues based on the TCGA, GSE28735, and GSE62452 datasets. We systematically explored the pan-cancer landscape of DE-ARGs. Most DE-ARGs also displayed differential expression trends in various tumors, which were strongly linked to favorable or unfavorable prognoses of patients with cancer, especially PC. Cluster analysis successfully identified three anoikis-associated subtypes for PC patients and two anoikis-associated subtypes for PNETs patients. The C1 subtype of PC patients showed a higher anoikis score, poorer prognosis, elevated expression of oncogenes, and lower level of immune cell infiltration, whereas the C2 subtype of PC patients had the exact opposite characteristics. We developed and validated a novel and accurate prognostic model for PC patients based on the expression traits of 13 DE-ARGs. In both training and test cohorts, the low-risk subpopulations had significantly longer overall survival than the high-risk subpopulations. Dysregulation of the tumor immune microenvironment could be responsible for the differences in clinical outcomes between low- and high-risk groups.ConclusionsThese findings provide fresh insights into the significance of anoikis in PC and PNETs. The identification of subtypes and construction of models have accelerated the progress of precision oncology.

Dataset Information

Locoregional Therapies and Remodeling of Tumor Microenvironment in Pancreatic Cancer.

Publications

Locoregional Therapies and Remodeling of Tumor Microenvironment in Pancreatic Cancer.

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