| First Author | Brownlie RJ | Year | 2019 |
| Journal | JCI Insight | Volume | 5 |
| PubMed ID | 31335326 | Mgi Jnum | J:298853 |
| Mgi Id | MGI:6472172 | Doi | 10.1172/jci.insight.127847 |
| Citation | Brownlie RJ, et al. (2019) Deletion of PTPN22 improves effector and memory CD8+ T cell responses to tumors. JCI Insight 5 |
| abstractText | Adoptive T cell therapy (ACT) has been established as an efficacious methodology for the treatment of cancer. Identifying targets to enhance the antigen recognition, functional capacity and longevity of T cells has the potential to broaden the applicability of these approaches in the clinic. We previously reported that targeting expression of phosphotyrosine phosphatase, non-receptor type (PTPN) 22 in effector CD8+ T cells enhances the efficacy of ACT for tumor clearance in mice. In the current work, we demonstrate that, upon ACT, PTPN22-deficient effector CD8+ T cells afford greater protection against tumors expressing very low affinity antigen, but do not survive long-term in vivo. Persistence of CD8+ T cells following tumor clearance is improved by ACT of memory phenotype cells that have a distinct metabolic phenotype as compared to effector T cells. Importantly, PTPN22-deficient T cells have comparable capacity to form long-lived memory cells in vivo but enhanced anti-tumor activity in vivo and effector responses ex vivo. These findings provide key insight into the regulation of effector and memory T cell responses in vivo, and indicate that PTPN22 is a rationale target to improve ACT for cancer. |
