| First Author | Nasiri E | Year | 2023 |
| Journal | Cells | Volume | 12 |
| Issue | 3 | PubMed ID | 36766797 |
| Mgi Jnum | J:337148 | Mgi Id | MGI:7436036 |
| Doi | 10.3390/cells12030456 | Citation | Nasiri E, et al. (2023) IL18 Receptor Signaling Inhibits Intratumoral CD8(+) T-Cell Migration in a Murine Pancreatic Cancer Model. Cells 12(3) |
| abstractText | In pancreatic ductal adenocarcinoma (PDAC), the infiltration of CD8(+) cytotoxic T cells (CTLs) is an important factor in determining prognosis. The migration pattern and interaction behavior of intratumoral CTLs are pivotal to tumor rejection. NLRP3-dependent proinflammatory cytokines IL-1beta and IL-18 play a prominent role for CTL induction and differentiation. Here, we investigate the effects of T-cellular IL-1R and IL-18R signaling for intratumoral T-cell motility. Murine adenocarcinoma cell line Panc02 was stably transfected with ovalbumin (OVA) and fluorophore H2B-Cerulean to generate PancOVA H2B-Cerulean tumor cells. Dorsal skinfold chambers (DSFC) were installed on wild-type mice, and PancOVA H2B-Cerulean tumor cells were implanted into the chambers. PancOVA spheroids were formed using the Corning((R)) Matrigel((R))-based 3D cell culture technique. CTLs were generated from OT-1 mice, Il1r(-/-) OT-1 mice, or Il18r(-/-) OT-1 mice and were marked with fluorophores. This was followed by the adoptive transfer of CTLs into tumor-bearing mice or the application into tumor spheroids. After visualization with multiphoton microscopy (MPM), Imaris software was used to perform T-cell tracking. Imaris analysis indicates a significantly higher accumulation of Il18r(-/-) CTLs in PancOVA tumors and a significant reduction in tumor volume compared to wild-type CTLs. Il18r(-/-) CTLs covered a longer distance (track displacement length) in comparison to wild-type (WT) CTLs, and had a higher average speed (mean track speed). The analysis of instantaneous velocity suggests a higher percentage of arrested tracks (arrests: <4 mum/min) for Il18r(-/-) CTLs. Our data indicate the contribution of IL-18R signaling to T-cell effector strength, warranting further investigation on phenomena such as intratumoral T-cell exhaustion. |
