Mutant KRAS drives immune evasion by sensitizing cytotoxic T-cells to activation-induced cell death in colorectal cancer
The roles of oncogenic KRAS in tumor immune evasion remain poorly understood. Here, mutant KRAS is identified as a key driver of tumor immune evasion in colorectal cancer (CRC). In human CRC specimens, a significant reduction in cytotoxic CD8+ T-cell tumor infiltration is found in patients with muta...
Gespeichert in:
| Hauptverfasser: | , , , , , , , , , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
04 January 2023
|
| In: |
Advanced science
Year: 2023, Jahrgang: 10, Heft: 6, Pages: 2203757 |
| ISSN: | 2198-3844 |
| DOI: | 10.1002/advs.202203757 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.1002/advs.202203757 Verlag, kostenfrei, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/advs.202203757 
|
| Verfasserangaben: | Huashan Liu, Zhenxing Liang, Sijing Cheng, Liang Huang, Wenxin Li, Chi Zhou, Xiaobin Zheng, Shujuan Li, Ziwei Zeng, Liang Kang |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1879623765 | ||
| 003 | DE-627 | ||
| 005 | 20240307025035.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240131s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1002/advs.202203757 |2 doi | |
| 035 | |a (DE-627)1879623765 | ||
| 035 | |a (DE-599)KXP1879623765 | ||
| 035 | |a (OCoLC)1425207258 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Liu, Huashan |e VerfasserIn |0 (DE-588)131778135X |0 (DE-627)1879626705 |4 aut | |
| 245 | 1 | 0 | |a Mutant KRAS drives immune evasion by sensitizing cytotoxic T-cells to activation-induced cell death in colorectal cancer |c Huashan Liu, Zhenxing Liang, Sijing Cheng, Liang Huang, Wenxin Li, Chi Zhou, Xiaobin Zheng, Shujuan Li, Ziwei Zeng, Liang Kang |
| 264 | 1 | |c 04 January 2023 | |
| 300 | |b Illustrationen | ||
| 300 | |a 15 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 31.01.2024 | ||
| 520 | |a The roles of oncogenic KRAS in tumor immune evasion remain poorly understood. Here, mutant KRAS is identified as a key driver of tumor immune evasion in colorectal cancer (CRC). In human CRC specimens, a significant reduction in cytotoxic CD8+ T-cell tumor infiltration is found in patients with mutant versus wild type KRAS. This phenomenon is confirmed by preclinical models of CRC, and further study showed KRAS mutant tumors exhibited poor response to anti-PD-1 and adoptive T-cell therapies. Mechanistic analysis revealed lactic acid derived from mutant KRAS-expressing tumor cells sensitized tumor-specific cytotoxic CD8+ T-cells to activation-induced cell death via NF-κB inactivation; this may underlie the inverse association between intratumoral cytotoxic CD8+ T-cells and KRAS mutation. Importantly, KRAS mutated tumor resistance to immunotherapies can be overcome by inhibiting KRAS or blocking lactic acid production. Together, this work suggests the KRAS-mediated immune program is an exploitable therapeutic approach for the treatment of patients with KRAS mutant CRC. | ||
| 650 | 4 | |a activation-induced cell death | |
| 650 | 4 | |a immune evasion | |
| 650 | 4 | |a mutant KRAS | |
| 700 | 1 | |a Liang, Zhenxing |e VerfasserIn |4 aut | |
| 700 | 1 | |a Cheng, Sijing |e VerfasserIn |4 aut | |
| 700 | 1 | |a Huang, Liang |e VerfasserIn |4 aut | |
| 700 | 1 | |a Li, Wenxin |e VerfasserIn |4 aut | |
| 700 | 1 | |a Zhou, Chi |e VerfasserIn |4 aut | |
| 700 | 1 | |a Zheng, Xiaobin |e VerfasserIn |4 aut | |
| 700 | 1 | |a Li, Shujuan |e VerfasserIn |4 aut | |
| 700 | 1 | |a Zeng, Ziwei |d 1995- |e VerfasserIn |0 (DE-588)1286632560 |0 (DE-627)1843156342 |4 aut | |
| 700 | 1 | |a Kang, Liang |e VerfasserIn |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Advanced science |d Weinheim : Wiley-VCH, 2014 |g 10(2023), 6, Seite 2203757 |h Online-Ressource |w (DE-627)817357777 |w (DE-600)2808093-2 |w (DE-576)425795926 |x 2198-3844 |7 nnas |a Mutant KRAS drives immune evasion by sensitizing cytotoxic T-cells to activation-induced cell death in colorectal cancer |
| 773 | 1 | 8 | |g volume:10 |g year:2023 |g number:6 |g pages:2203757 |g extent:15 |a Mutant KRAS drives immune evasion by sensitizing cytotoxic T-cells to activation-induced cell death in colorectal cancer |
| 856 | 4 | 0 | |u https://doi.org/10.1002/advs.202203757 |x Verlag |x Resolving-System |z kostenfrei |3 Volltext |
| 856 | 4 | 0 | |u https://onlinelibrary.wiley.com/doi/abs/10.1002/advs.202203757 |x Verlag |z kostenfrei |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20240131 | ||
| 993 | |a Article | ||
| 994 | |a 2023 | ||
| 998 | |g 1286632560 |a Zeng, Ziwei |m 1286632560:Zeng, Ziwei |d 60000 |e 60000PZ1286632560 |k 0/60000/ |p 9 | ||
| 999 | |a KXP-PPN1879623765 |e 4472602504 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"note":["Gesehen am 31.01.2024"],"type":{"media":"Online-Ressource","bibl":"article-journal"},"recId":"1879623765","language":["eng"],"person":[{"display":"Liu, Huashan","roleDisplay":"VerfasserIn","role":"aut","family":"Liu","given":"Huashan"},{"roleDisplay":"VerfasserIn","display":"Liang, Zhenxing","role":"aut","family":"Liang","given":"Zhenxing"},{"role":"aut","display":"Cheng, Sijing","roleDisplay":"VerfasserIn","given":"Sijing","family":"Cheng"},{"roleDisplay":"VerfasserIn","display":"Huang, Liang","role":"aut","family":"Huang","given":"Liang"},{"given":"Wenxin","family":"Li","role":"aut","roleDisplay":"VerfasserIn","display":"Li, Wenxin"},{"roleDisplay":"VerfasserIn","display":"Zhou, Chi","role":"aut","family":"Zhou","given":"Chi"},{"family":"Zheng","given":"Xiaobin","roleDisplay":"VerfasserIn","display":"Zheng, Xiaobin","role":"aut"},{"roleDisplay":"VerfasserIn","display":"Li, Shujuan","role":"aut","family":"Li","given":"Shujuan"},{"display":"Zeng, Ziwei","roleDisplay":"VerfasserIn","role":"aut","family":"Zeng","given":"Ziwei"},{"display":"Kang, Liang","roleDisplay":"VerfasserIn","role":"aut","family":"Kang","given":"Liang"}],"title":[{"title_sort":"Mutant KRAS drives immune evasion by sensitizing cytotoxic T-cells to activation-induced cell death in colorectal cancer","title":"Mutant KRAS drives immune evasion by sensitizing cytotoxic T-cells to activation-induced cell death in colorectal cancer"}],"physDesc":[{"extent":"15 S.","noteIll":"Illustrationen"}],"relHost":[{"physDesc":[{"extent":"Online-Ressource"}],"origin":[{"dateIssuedDisp":"2014-","publisher":"Wiley-VCH","dateIssuedKey":"2014","publisherPlace":"Weinheim"}],"id":{"issn":["2198-3844"],"eki":["817357777"],"doi":["10.1002/(ISSN)2198-3844"],"zdb":["2808093-2"]},"disp":"Mutant KRAS drives immune evasion by sensitizing cytotoxic T-cells to activation-induced cell death in colorectal cancerAdvanced science","note":["Gesehen am 21.10.2022"],"type":{"bibl":"periodical","media":"Online-Ressource"},"language":["eng"],"recId":"817357777","pubHistory":["1.2014 (Dezember)-"],"part":{"issue":"6","pages":"2203757","year":"2023","extent":"15","text":"10(2023), 6, Seite 2203757","volume":"10"},"title":[{"title":"Advanced science","title_sort":"Advanced science"}]}],"name":{"displayForm":["Huashan Liu, Zhenxing Liang, Sijing Cheng, Liang Huang, Wenxin Li, Chi Zhou, Xiaobin Zheng, Shujuan Li, Ziwei Zeng, Liang Kang"]},"origin":[{"dateIssuedDisp":"04 January 2023","dateIssuedKey":"2023"}],"id":{"doi":["10.1002/advs.202203757"],"eki":["1879623765"]}} | ||
| SRT | |a LIUHUASHANMUTANTKRAS0420 | ||