| First Author | Savid-Frontera C | Year | 2022 |
| Journal | Front Immunol | Volume | 13 |
| Pages | 971001 | PubMed ID | 36330506 |
| Mgi Jnum | J:330727 | Mgi Id | MGI:7383636 |
| Doi | 10.3389/fimmu.2022.971001 | Citation | Savid-Frontera C, et al. (2022) Exploring the immunomodulatory role of virtual memory CD8+ T cells: Role of IFN gamma in tumor growth control. Front Immunol 13:971001 |
| abstractText | Virtual memory CD8<sup>+</sup> T cells (T<sub>VM</sub>) have been described as cells with a memory-like phenotype but without previous antigen (Ag) exposure. T<sub>VM</sub> cells have the ability to respond better to innate stimuli rather than by TCR engagement, producing large amounts of interferon gamma (IFNgamma) after stimulation with interleukin (IL)-12 plus IL-18. As a result of the phenotypic similarity, T<sub>VM</sub> cells have been erroneously included in the central memory T cell subset for many years. However, they can now be discriminated <i>via</i> the CD49d receptor, which is up-regulated only on conventional memory T cells (T<sub>MEM</sub>) and effector T cells (T<sub>EFF</sub>) after specific cognate Ag recognition by a TCR. In this work we show that systemic expression of IL-12 plus IL-18 induced an alteration in the normal T<sub>VM</sub> vs T<sub>MEM</sub>/T<sub>EFF</sub> distribution in secondary lymphoid organs and a preferential enrichment of T<sub>VM</sub> cells in the melanoma (B16) and the pancreatic ductal adenocarcinoma (KPC) tumor models. Using our KPC bearing OT-I mouse model, we observed a significant increase in CD8<sup>+</sup> T cell infiltrating the tumor islets after IL-12+IL-18 stimulation with a lower average speed when compared to those from control mice. This finding indicates a stronger interaction of T cells with tumor cells after cytokine stimulation. These results correlate with a significant reduction in tumor size in both tumor models in IL-12+IL-18-treated OT-I mice compared to control OT-I mice. Interestingly, the absence of IFNgamma completely abolished the high antitumor capacity induced by IL-12+IL-18 expression, indicating an important role for these cytokines in early tumor growth control. Thus, our studies provide significant new information that indicates an important role of T<sub>VM</sub> cells in the immune response against cancer. |
