Dapl1 controls NFATc2 activation to regulate CD8+ T cell exhaustion and responses in chronic infection and cancer View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2022-06-30

AUTHORS

Lele Zhu, Xiaofei Zhou, Meidi Gu, Jiseong Kim, Yanchuan Li, Chun-Jung Ko, Xiaoping Xie, Tianxiao Gao, Xuhong Cheng, Shao-Cong Sun

ABSTRACT

CD8+ T cells are central mediators of immune responses against infections and cancer. Here we identified Dapl1 as a crucial regulator of CD8+ T cell responses to cancer and infections. Dapl1 deficiency promotes the expansion of tumour-infiltrating effector memory-like CD8+ T cells and prevents their functional exhaustion, coupled with increased antitumour immunity and improved efficacy of adoptive T cell therapy. Dapl1 controls activation of NFATc2, a transcription factor required for the effector function of CD8+ T cells. Although NFATc2 mediates induction of the immune checkpoint receptor Tim3, competent NFATc2 activation prevents functional exhaustion of CD8+ T cells. Interestingly, exhausted CD8+ T cells display attenuated NFATc2 activation due to Tim3-mediated feedback inhibition; Dapl1 deletion rescues NFATc2 activation and thereby prevents dysfunction of exhausted CD8+ T cells in chronic infection and cancer. These findings establish Dapl1 as a crucial regulator of CD8+ T cell immunity and a potential target for cancer immunotherapy. More... »

PAGES

1165-1176

References to SciGraph publications

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  • Identifiers

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    http://scigraph.springernature.com/pub.10.1038/s41556-022-00942-8

    DOI

    http://dx.doi.org/10.1038/s41556-022-00942-8

    DIMENSIONS

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    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/35773432


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    44 activation
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    59 deficiency
    60 deletion
    61 display
    62 dysfunction
    63 effector functions
    64 efficacy
    65 exhausted CD8
    66 exhaustion
    67 expansion
    68 factors
    69 feedback inhibition
    70 findings
    71 function
    72 functional exhaustion
    73 immune response
    74 immunity
    75 immunotherapy
    76 improved efficacy
    77 induction
    78 infection
    79 inhibition
    80 mediators
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    82 potential target
    83 prevents dysfunction
    84 regulator
    85 response
    86 target
    87 therapy
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