| First Author | Slusny B | Year | 2024 |
| Journal | Cancers (Basel) | Volume | 17 |
| Issue | 1 | PubMed ID | 39796680 |
| Mgi Jnum | J:361323 | Mgi Id | MGI:7854112 |
| Doi | 10.3390/cancers17010051 | Citation | Slusny B, et al. (2024) Optimized Spheroid Model of Pancreatic Cancer Demonstrates Influence of Macrophage-T Cell Interaction for Intratumoral T Cell Motility. Cancers (Basel) 17(1) |
| abstractText | BACKGROUND: Most spheroid models use size measurements as a primary readout parameter; some models extend analysis to T cell infiltration or perform caspase activation assays. However, to our knowledge, T cell motility analysis is not regularly included as an endpoint in imaging studies on cancer spheroids. METHODS: Here, we intend to demonstrate that motility analysis of macrophages and T cells is a valuable functional endpoint for studies on molecular interventions in the tumor microenvironment. In particular, T cell migration analysis represents the final step of effector function, as T cells engage with targets cells upon cytotoxic interaction, which is represented by an arrest within the spheroid volume. Therefore, T cell arrest is a novel readout parameter of T cell effector function in spheroids. RESULTS: Here, we demonstrate that incubation of macrophages with nigericin for NLRP3 activation increases T cell velocity, but results in decreased T cellular arrest. This is paralleled by reduced rejection kinetics of pancreatic cancer spheroids in the presence of antigen-dependent T cells and nigericin-treated macrophages. Our model demonstrates consistent changes in T cell motility upon coculturing of T cells and tumors cells with macrophages, including influences of molecular interventions such as NLRP3 activation. CONCLUSIONS: Motility analysis using a spheroid model of pancreatic cancer is a more sophisticated alternative to in vitro cytotoxicity assays measuring spheroid size. Ultimately, an optimized spheroid model might replace at least some aspects of animal experiments investigating T cell effector function. |
