دورية أكاديمية
VEGF-A drives TOX-dependent T cell exhaustion in anti-PD-1-resistant microsatellite stable colorectal cancers
| العنوان: | VEGF-A drives TOX-dependent T cell exhaustion in anti-PD-1-resistant microsatellite stable colorectal cancers |
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| المؤلفون: | Kim, Chang Gon, Jang, Mi, Kim, Youngun, Leem, Galam, Kim, Kyung Hwan, Lee, Hoyoung, Kim, Tae-Shin, Choi, Seong Jin, Kim, Hyung-Don, Han, Ji Won, Kwon, Minsuk, Kim, Jong Hoon, Lee, Andrew J., Nam, Su Kyung, Bae, Seok-Joo, Lee, Sat Byol, Shin, Sang Joon, Park, Sung Ho, Ahn, Joong Bae, Jung, Inkyung, Lee, Kang Young, Park, Su Hyung, Kim, Hoguen, Min, Byung Soh, Shin, Eui-Cheol |
| بيانات النشر: | American Association for the Advancement of Science |
| سنة النشر: | 2019 |
| المجموعة: | ScholarWorks@UNIST (Ulsan National Institute of Science and Technology) |
| الوصف: | Although immune checkpoint blockade therapies have demonstrated clinical efficacy in cancer treatment, harnessing this strategy is largely encumbered by resistance in multiple cancer settings. Here, we show that tumor-infiltrating T cells are severely exhausted in the microsatellite stable (MSS) colorectal cancer (CRC), a representative example of PD-1 blockade-resistant tumors. In MSS CRC, we found wound healing signature to be up-regulated and that T cell exhaustion is driven by vascular endothelial growth factor-A (VEGF-A). We report that VEGF-A induces the expression of transcription factor TOX in T cells to drive exhaustion-specific transcription program in T cells. Using a combination of in vitro, ex vivo, and in vivo mouse studies, we demonstrate that combined blockade of PD-1 and VEGF-A restores the antitumor functions of T cells, resulting in better control of MSS CRC tumors. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| تدمد: | 2470-9468 |
| العلاقة: | SCIENCE IMMUNOLOGY, v.4, no.41, pp.eaay0555; https://scholarworks.unist.ac.kr/handle/201301/30960Test; 34242; 2-s2.0-85074742367; 000516638800007; https://immunology.sciencemag.org/content/4/41/eaay0555Test |
| DOI: | 10.1126/sciimmunol.aay0555 |
| الإتاحة: | https://doi.org/10.1126/sciimmunol.aay0555Test https://scholarworks.unist.ac.kr/handle/201301/30960Test https://immunology.sciencemag.org/content/4/41/eaay0555Test |
| رقم الانضمام: | edsbas.638619DC |
| قاعدة البيانات: | BASE |
| تدمد: | 24709468 |
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| DOI: | 10.1126/sciimmunol.aay0555 |