Brownlie, RJ orcid.org/0000-0003-4897-1044, Wright, D, Zamoyska, R et al. (1 more author) (2019) Deletion of PTPN22 improves effector and memory CD8+ T cell responses to tumors. JCI Insight, 4 (16). e127847. ISSN 2379-3708
Abstract
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2019, Brownlie et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License. |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cancer and Pathology (LICAP) > Infection and Immunity (Leeds) |
Funding Information: | Funder Grant number Cancer Research UK C55663/A23269 |
Depositing User: | Symplectic Publications |
Date Deposited: | 26 Jul 2019 10:39 |
Last Modified: | 25 Jun 2023 21:55 |
Status: | Published |
Publisher: | American Society for Clinical Investigation |
Identification Number: | 10.1172/jci.insight.127847 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:148996 |
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