کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10748510 | 1050274 | 2016 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Transient exposure to proteins SOX2, Oct-4, and NANOG immortalizes exhausted tumor-infiltrating CTLs
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کلمات کلیدی
CTLACTIPSCOct4Sox2NANOGSignal transducer and activator of transcription proteinSTAT - آمارTIL - بهNuclear delivery - تحویل هسته ایTumor infiltrating lymphocytes - تومور لنفوسیت ها نفوذ می کندTILS - جریان بداخلDouble negative T cells - دو سلول T منفیInduced pluripotent stem cell - سلول های بنیادی پلوروپتوژن منجر شده استSON - فرزند پسرcytotoxic T lymphocyte - لنفوسیت T سیتوتوکسیک
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Adoptive cell transfer therapy (ACT) is one of the most promising immunotherapies against cancer, using tumor-infiltrating lymphocytes (TILs) expanded in vitro. Tumor-infiltrating cytotoxic T lymphocytes (TICTLs) play a prominent role in cancer control. TILs terminally differentiate in response to immunosuppressive environments within tumors, and thus are slow to expand and challenging to maintain both in vitro and in patients. To reverse this exhaustion, we utilize a nuclear protein delivery system that exposes TICTLs to the SOX2, Oct-4, and NANOG (SON) proteins. Unlike activated naïve CTLs (effector CTLs), TICTLs respond favorably to SON treatment, exhibiting steady proliferation and extended survivability independent of cytokine and antigen stimulation. Though TICTLs treated with SON (STICTLs) still express T cell receptors as well as other critical downstream components, they are unresponsive to antigen challenge, suggesting that SON treatment regresses TICTLs into a state similar to that of an early double negative T cell. Our findings indicate the TICTL response to SON proteins is unique when compared to effector CTLs, suggesting TICTLs may be sensitive to regulation by other lineage-specific transcription factors and opening a promising new avenue into cancer immunotherapy. To our knowledge, this is the first report on lineage reprogramming of TILs using protein stem cell transcription factors delivered directly to the nucleus.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 473, Issue 4, 13 May 2016, Pages 1255-1260
Journal: Biochemical and Biophysical Research Communications - Volume 473, Issue 4, 13 May 2016, Pages 1255-1260
نویسندگان
Anjuli Bhadurihauck, Lei Li, Qianqian Li, Jianjun Wang, Zhengguo Xiao,