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SHP-1: the next checkpoint target for cancer immunotherapy?

Watson, Heulwen Angharad, Wehenkel, Sophie, Matthews, James and Ager, Elizabeth ORCID: 2016. SHP-1: the next checkpoint target for cancer immunotherapy? Biochemical Society Transactions 44 (2) , pp. 356-362. 10.1042/BST20150251

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The immense power of the immune system is harnessed in healthy individuals by a range of negative regulatory signals and checkpoints. Manipulating these checkpoints through inhibition has resulted in striking immune-mediated clearance of otherwise untreatable tumours and metastases; unfortunately, not all patients respond to treatment with the currently available inhibitors of cytotoxic T-lymphocyteassociated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1). Combinatorial studies using both anti-CTLA-4 and anti-PD-1 demonstrate synergistic effects of targeting multiple checkpoints, paving the way for other immune checkpoints to be targeted. Src homology 2 domain-containing protein tyrosine phosphatase 1 (SHP-1) is a widely expressed inhibitory protein tyrosine phosphatase (PTP). In T-cells, it is a negative regulator of antigen-dependent activation and proliferation. It is a cytosolic protein, and therefore not amenable to antibody-mediated therapies, but its role in activation and proliferation makes it an attractive target for genetic manipulation in adoptive transfer strategies, such as chimeric antigen receptor (CAR) T-cells. This review will discuss the potential value of SHP-1 inhibition in future tumour immunotherapy.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
Publisher: Portland Press
ISSN: 0300-5127
Funders: Wellcome Trust, Medical Research Council UK
Date of First Compliant Deposit: 23 May 2016
Date of Acceptance: 5 February 2016
Last Modified: 05 May 2023 01:28

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