東華大學圖書館 |

語系: 繁體中文

說明(常見問題)

回圖書館首頁

手機版館藏查詢

登入

回首頁

切換: 標籤 | MARC模式 | ISBD

The Role of the NKR-P1B:Clr-b Recogn...

Tanaka, Miho.

FindBook

Google Book

Amazon

博客來

The Role of the NKR-P1B:Clr-b Recognition Axis in Oncogenic Transformation and Cancer Immunosurveillance.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	The Role of the NKR-P1B:Clr-b Recognition Axis in Oncogenic Transformation and Cancer Immunosurveillance./
作者:	Tanaka, Miho.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2019,
面頁冊數:	166 p.
附註:	Source: Dissertations Abstracts International, Volume: 81-02, Section: B.
Contained By:	Dissertations Abstracts International81-02B.
標題:	Immunology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=13420535
ISBN:	9781085755825

The Role of the NKR-P1B:Clr-b Recognition Axis in Oncogenic Transformation and Cancer Immunosurveillance.
Tanaka, Miho.

The Role of the NKR-P1B:Clr-b Recognition Axis in Oncogenic Transformation and Cancer Immunosurveillance. - Ann Arbor : ProQuest Dissertations & Theses, 2019 - 166 p.

Source: Dissertations Abstracts International, Volume: 81-02, Section: B.

Thesis (Ph.D.)--University of Toronto (Canada), 2019.

This item must not be sold to any third party vendors.

Natural killer (NK) cells play important role in tumour elimination, virus control, transplant rejection, and the elimination of cells going under genotoxic or cellular stress. They facilitate this innate immune recognition by detecting changes in ligand expression on target cells mediated via germline-encoded NK cell receptors. Here, we elucidate the role of MHC-I-independent NKR-P1B:Clr-b receptor-ligand interactions in the detection of oncogenic transformation by NK cells. Ras and c-Myc proto-oncogene overexpression were found to promote a real-time loss of Clr-b on mouse fibroblasts and leukemia cells. Ras-driven Clr-b downregulation was mediated in part via the Raf/MEK/ERK and PI3K pathways, regulated at multiple levels, including the Clrb (Clec2d) promoter, nascent Clr-b transcripts, and cell surface Clr-b protein. Clr-b downregulation on leukemia cells in turn diminished recognition of the target cells via the NKR-P1B inhibitory receptor, augmented cytotoxicity mediated by NKR-P1B+ NK cells in vitro, and enhanced rejection by WT mice in vivo. Interestingly, genetic ablation of either one (Clr-b+/-) or two Clr-b alleles (Clr-b-/-) enhanced survival of Eμ-cMyc transgenic mice in a primary lymphoma model, despite preferential rejection of Clr-b-/- hematopoietic cells previously observed following adoptive transfer into naive wild-type mice in vivo. Collectively, these findings suggest that the inhibitory NKR-P1B:Clr-b axis plays a beneficial role in the innate detection of oncogenic transformation via NK cell-mediated cancer immunosurveillance, in addition to a pathological role in the immune escape of primary lymphoma cells in Eμ-cMyc mice in vivo.In an attempt to discover novel pathways involved in Clr-b ligand regulation, we initiated genome-wide loss-of-function screening in lymphoma cells sorted for high or low Clr-b levels. Validation analysis of potential targets identified two genes with oncogenic properties, Ddx6 and PPARα, that are potentially involved in Clr-b downregulation.These results provide a model for the human inhibitory NKR-P1A:LLT1 system, a human homolog for NKR-P1B:Clr-b, in cancer immunosurveillance in lymphoma patients, and suggest it may represent a target for immune checkpoint therapy.

ISBN: 9781085755825Subjects--Topical Terms:

611031
Immunology.
Subjects--Index Terms:

Cancer

The Role of the NKR-P1B:Clr-b Recognition Axis in Oncogenic Transformation and Cancer Immunosurveillance.
LDR:03520nmm a2200421 4500 001 2272333
005 20201105110023.5
008 220629s2019 ||||||||||||||||| ||eng d
020 $a 9781085755825
035 $a (MiAaPQ)AAI13420535
035 $a AAI13420535
040 $a MiAaPQ $c MiAaPQ
100 1 $a Tanaka, Miho. $3 3549767
245 1 4 $a The Role of the NKR-P1B:Clr-b Recognition Axis in Oncogenic Transformation and Cancer Immunosurveillance.
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2019
300 $a 166 p.
500 $a Source: Dissertations Abstracts International, Volume: 81-02, Section: B.
500 $a Advisor: Carlyle, James R.
502 $a Thesis (Ph.D.)--University of Toronto (Canada), 2019.
506 $a This item must not be sold to any third party vendors.
520 $a Natural killer (NK) cells play important role in tumour elimination, virus control, transplant rejection, and the elimination of cells going under genotoxic or cellular stress. They facilitate this innate immune recognition by detecting changes in ligand expression on target cells mediated via germline-encoded NK cell receptors. Here, we elucidate the role of MHC-I-independent NKR-P1B:Clr-b receptor-ligand interactions in the detection of oncogenic transformation by NK cells. Ras and c-Myc proto-oncogene overexpression were found to promote a real-time loss of Clr-b on mouse fibroblasts and leukemia cells. Ras-driven Clr-b downregulation was mediated in part via the Raf/MEK/ERK and PI3K pathways, regulated at multiple levels, including the Clrb (Clec2d) promoter, nascent Clr-b transcripts, and cell surface Clr-b protein. Clr-b downregulation on leukemia cells in turn diminished recognition of the target cells via the NKR-P1B inhibitory receptor, augmented cytotoxicity mediated by NKR-P1B+ NK cells in vitro, and enhanced rejection by WT mice in vivo. Interestingly, genetic ablation of either one (Clr-b+/-) or two Clr-b alleles (Clr-b-/-) enhanced survival of Eμ-cMyc transgenic mice in a primary lymphoma model, despite preferential rejection of Clr-b-/- hematopoietic cells previously observed following adoptive transfer into naive wild-type mice in vivo. Collectively, these findings suggest that the inhibitory NKR-P1B:Clr-b axis plays a beneficial role in the innate detection of oncogenic transformation via NK cell-mediated cancer immunosurveillance, in addition to a pathological role in the immune escape of primary lymphoma cells in Eμ-cMyc mice in vivo.In an attempt to discover novel pathways involved in Clr-b ligand regulation, we initiated genome-wide loss-of-function screening in lymphoma cells sorted for high or low Clr-b levels. Validation analysis of potential targets identified two genes with oncogenic properties, Ddx6 and PPARα, that are potentially involved in Clr-b downregulation.These results provide a model for the human inhibitory NKR-P1A:LLT1 system, a human homolog for NKR-P1B:Clr-b, in cancer immunosurveillance in lymphoma patients, and suggest it may represent a target for immune checkpoint therapy.
590 $a School code: 0779.
650 4 $a Immunology. $3 611031
650 4 $a Oncology. $3 751006
650 4 $a Medicine. $3 641104
650 4 $a Physiology. $3 518431
650 4 $a Public health. $3 534748
650 4 $a Epidemiology. $3 568544
653 $a Cancer
653 $a Clr-b
653 $a Immunology
653 $a Immunotherapy
653 $a Natural killer cells
653 $a NKR-P1B
690 $a 0982
690 $a 0992
690 $a 0564
690 $a 0766
690 $a 0573
690 $a 0719
710 2 $a University of Toronto (Canada). $b Immunology. $3 3193210
773 0 $t Dissertations Abstracts International $g 81-02B.
790 $a 0779
791 $a Ph.D.
792 $a 2019
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=13420535