The new paper A tumor microenvironment model of pancreatic cancer to elucidate responses toward immunotherapy by Verena Kast, Ali Nadernezhad, Dagmar Pette, Anastasiia Gabrielyan, Maximilian Fusenig, Kim C Honselmann, Daniel E Stange, Carsten Werner, and Daniela Loessner introduces a pre-clinical platform of pancreatic cancer that reconstruct the extracellular, cellular, and biomechanical elements of tumor tissues to assess responses toward immunotherapy.
Pancreatic cancer is a devastating malignancy with minimal treatment options. Standard-of-care therapy, including surgery and chemotherapy, is unsatisfactory, and therapies harnessing the immune system have been unsuccessful in clinical trials. Currently, most immunotherapies are tested in genetically engineered mouse models and patient-derived xenografts, presenting poor clinical translation because of the lack of human immune components.
To address this limitation, they established a 3D hydrogel model of human pancreatic cancer based on star-shaped poly(ethylene glycol)-heparin that recreates the stiffness of tumor-bearing tissue, enables cell-matrix interactions, cellular crosstalk, and replicates components of the immunosuppressive tumor microenvironment of the disease. Exploring the potentials of this platform, combining the novel CD11b agonist ADH-503 with anti-PD-1 immunotherapy and chemotherapy led to a significant reduction in tumor cell viability, proliferation, metabolic activity, immunomodulation, and secretion of immunosuppressive and tumor growth-promoting cytokines. As such, they provide a novel, rationally designed in vitro platform for screening novel immunomodulatory therapeutic strategies for patients diagnosed with PDAC.
The paper was published in Advanced Healthcare Materials.

01.12.2022

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