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Elucidating the mechanisms of resistance to immunotherapy and developing strategies to improve its efficacy are challenging goals. Bioinformatics analysis demonstrates that high CDK6 expression in melanoma is associated with poor progression-free survival of patients receiving single-agent immunotherapy. Depletion of CDK6 or cyclin D3 (but not of CDK4, cyclin D1, or D2) in cells of the tumor microenvironment inhibits tumor growth. CDK6 depletion reshapes the tumor immune microenvironment, and the host anti-tumor effect depends on cyclin D3/CDK6-expressing CD8+ and CD4+ T cells. This occurs by CDK6 phosphorylating and increasing the activities of PTP1B and T cell protein tyrosine phosphatase (TCPTP), which, in turn, decreases tyrosine phosphorylation of CD3ζ, reducing the signal transduction for T cell activation. Administration of a PTP1B and TCPTP inhibitor prove more efficacious than using a CDK6 degrader in enhancing T cell-mediated immunotherapy. Targeting protein tyrosine phosphatases (PTPs) might be an effective strategy for cancer patients who resist immunotherapy treatment.
Pubmed ID: 37000627 RIS Download
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View all literature mentionsIn vivo imaging software which facilitates workflow for in vivo optical, X-ray and microCT image acquisition, analysis and data organization.
View all literature mentionsWeb server for comprehensive analysis of tumor infiltrating immune cells. Web tool for systematical analysis of immune infiltrates across diverse cancer types. Allows users to input function specific parameters, with resulting figures dynamically displayed to access tumor immunological, clinical, and genomic features.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
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Mus musculus with name B6.SJL-Ptprca Pepc
This monoclonal targets Human/Mouse/Rat TC-PTP MAb (Clone 252294)
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View all literature mentionsThis monoclonal targets CD197
View all literature mentionsThis monoclonal targets CD45RO
View all literature mentionsThis monoclonal targets CD45RA
View all literature mentionsThis monoclonal targets CD34
View all literature mentionsThis monoclonal targets CD8
View all literature mentionsThis monoclonal targets CD4
View all literature mentionsThis isotype control targets KLH
View all literature mentionsThis monoclonal targets CD8α
View all literature mentionsThis monoclonal targets FOXP3
View all literature mentionsThis monoclonal targets Granzyme B
View all literature mentionsThis monoclonal targets IL-2
View all literature mentionsThis monoclonal targets IFN-gamma
View all literature mentionsThis monoclonal targets Phospho-CD247 (CD3 zeta) (Tyr142)
View all literature mentionsThis monoclonal targets TNF
View all literature mentionsThis monoclonal targets NK-1.1
View all literature mentionsThis monoclonal targets Ly-6G
View all literature mentionsThis monoclonal targets CD206
View all literature mentionsThis monoclonal targets Ly-6C
View all literature mentionsThis monoclonal targets CD45R
View all literature mentionsThis monoclonal targets F4/80
View all literature mentionsThis monoclonal targets CD11c
View all literature mentionsThis monoclonal targets Mouse CD11b
View all literature mentionsThis monoclonal targets CD45
View all literature mentionsThis monoclonal targets TCR beta chain
View all literature mentionsThis monoclonal targets CD62L
View all literature mentionsThis monoclonal targets CD8a
View all literature mentionsThis monoclonal targets CD4
View all literature mentionsThis monoclonal targets SHP2
View all literature mentionsThis monoclonal targets SHP-1
View all literature mentionsThis polyclonal targets Phospho-Rb (Ser780)
View all literature mentionsThis polyclonal targets His-probe (H-15)
View all literature mentionsThis monoclonal targets GAPDH
View all literature mentionsThis unknown targets GST
View all literature mentionsThis monoclonal targets α-Tubulin
View all literature mentionsThis monoclonal targets Wip1 (F-10)
View all literature mentionsThis polyclonal targets CD247
View all literature mentionsThis monoclonal targets p-Tyr (PY99)
View all literature mentionsThis monoclonal targets Mitotic Human HeLa Cell cytosolic lysate
View all literature mentionsThis polyclonal targets PTPN2
View all literature mentionsThis monoclonal targets PTP1B
View all literature mentionsThis polyclonal targets PTP1B
View all literature mentionsThis monoclonal targets CCND3
View all literature mentionsThis monoclonal targets Cyclin D2
View all literature mentionsThis polyclonal targets Cyclin D1 / bcl-1 (G1-Cyclin & Mantle Cell Lymphoma Marker)
View all literature mentionsThis monoclonal targets Cdk4
View all literature mentionsThis monoclonal targets CDK2
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