Inhibition of CDK4/6 Promotes CD8 T-cell Memory Formation.
Inhibition of CDK4/6 Promotes CD8 T-cell Memory Formation.
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DOI：
10.1158/2159-8290.cd-20-1540
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发表时间：
2021-10
期刊：
影响因子：
28.2
通讯作者：
Dougan SK
中科院分区：
文献类型：
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作者：
Heckler M;Ali LR;Clancy-Thompson E;Qiang L;Ventre KS;Lenehan P;Roehle K;Luoma A;Boelaars K;Peters V;McCreary J;Boschert T;Wang ES;Suo S;Marangoni F;Mempel TR;Long HW;Wucherpfennig KW;Dougan M;Gray NS;Yuan GC;Goel S;Tolaney SM;Dougan SK
CDK4/6 inhibitors are approved to treat breast cancer and are in trials for other malignancies. We examined CDK4/6 inhibition in mouse and human CD8 T cells during early stages of activation. Mice receiving tumor-specific CD8 T cells treated with CDK4/6 inhibitors displayed increased T cell persistence and immunologic memory. CDK4/6 inhibition upregulated Mxd4, a negative regulator of Myc, in both mouse and human CD8 T cells. Silencing of Mxd4 or Myc in mouse CD8 T cells demonstrated the importance of this axis for memory formation. We used single cell transcriptional profiling and TCR clonotype tracking to evaluate recently activated human CD8 T cells in breast cancer patients before and during treatment with either palbociclib or abemaciclib. CDK4/6 inhibitor therapy in humans increases the frequency of CD8 memory precursors and downregulates their expression of MYC target genes, suggesting that CDK4/6 inhibitors in cancer patients may augment long-term protective immunity.
