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「全米図書賞」作家 多和田葉子さん 朗読イベントに出演

去年、アメリカで最も権威のある文学賞を受賞した、ドイツ在住の作家、多和田葉子さんが、一時帰国して朗読イベントに出演し、声で伝えることばのおもしろさを表現しました...

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ニュース一覧

Tumor-specific CD8 T cell dysfunction is a differentiation state distinct from the functional effector or memory T cell states. Here we identify the nuclear factor, Thymocyte selection-associated HMG box protein, TOX, as a critical regulator of tumor-specific T cell (TST) differentiation. We show that TOX is highly expressed in dysfunctional TST from tumors and in exhausted T cells in chronic viral infection. TOX expression is driven by chronic TCR stimulation and NFAT activation. Ectopic expression of TOX in effector T cells in vitro induced a transcriptional program associated with T cell exhaustion. Conversely, Tox deletion in TST in tumors abrogated the exhaustion program: Tox-deleted TST did not upregulate inhibitory receptors (e.g. Pdcd1, Entpd1, Havcr2, Cd244, Tigit), whose chromatin remained largely inaccessible, and retained high expression of transcription factors such as TCF1. Despite their normal, "non-exhausted" immunophenotype, Tox-deleted TST remained dysfunctional, revealing that the regulation of inhibitory receptor expression is uncoupled from the loss of effector function. Importantly, while Tox-deleted CD8 T cells differentiated normally to effector and memory states in response to acute infection, Tox-deleted TST failed to persist in tumors. We hypothesize that the TOX-induced exhaustion program serves to prevent T cell overstimulation and activation-induced cell death in settings of chronic antigen stimulation such as cancer.
PMID: 31207604 [PubMed - as supplied by publisher]
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