A 3D pancreatic tumor model to study T cell infiltration. (27th October 2021)

• Record Type: Journal Article
• Authors: Mollica, Hilaria; Teo, Yi Juan; Tan, Alrina Shin Min; Tan, Damien Zhi Ming; Decuzzi, Paolo; Pavesi, Andrea; Adriani, Giulia
• Is Part Of: Biomaterials science. Volume 9:Number 22(2021)
• Page Start: 7420
• Page End: 7431
• Publication Date: 2021-10-27
• Subjects: Biomedical materials -- Periodicals; 610.28
• DOI: 10.1039/d1bm00210d
• Languages: English
• ISSNs: 2047-4830

Abstract

Abstract : Human T cell infiltration across the endothelium in a 3-dimensional pancreatic tumor model in relation to activation and cellular components. Abstract : The desmoplastic nature of the pancreatic ductal adenocarcinoma (PDAC) tumor microenvironment (TME) prevents the infiltration of T cells and the penetration of chemotherapeutic drugs, posing a challenge to the validation of targeted therapies, including T cell immunotherapies. We present an in vitro 3D PDAC-TME model to observe and quantify T cell infiltration across the vasculature. In a three-channel microfluidic device, PDAC cells are cultured in a collagen matrix in the central channel surrounded, on one side, by endothelial cells (ECs) to mimic a blood vessel and, on the opposite side, by pancreatic stellate cells (PSCs) to simulate exocrine pancreas. The migration of T cells toward the tumor is quantified based on their activation state and TME composition. The presence of EC-lining drastically reduces T cell infiltration, confirming the essential role of the vasculature in controlling T cell trafficking. We show that activated T cells migrate ∼50% more than the not-activated ones toward the cancer cells. Correspondingly, in the absence of cancer cells, both activated and not-activated T cells present similar migration toward the PSCs. The proposed approach could help researchers in testing and optimizing immunotherapies for pancreatic cancer.