دورية أكاديمية
NKG2A and HLA-E define an alternative immune checkpoint axis in bladder cancer.
| العنوان: | NKG2A and HLA-E define an alternative immune checkpoint axis in bladder cancer. |
|---|---|
| المؤلفون: | Salomé, Bérengère1,2 (AUTHOR), Sfakianos, John P.3 (AUTHOR), Ranti, Daniel1,2,3 (AUTHOR), Daza, Jorge1,2,3 (AUTHOR), Bieber, Christine1,2,3 (AUTHOR), Charap, Andrew1,2,3 (AUTHOR), Hammer, Christian4,5 (AUTHOR), Banchereau, Romain6 (AUTHOR), Farkas, Adam M.1,7 (AUTHOR), Ruan, Dan Fu1,2 (AUTHOR), Izadmehr, Sudeh7 (AUTHOR), Geanon, Daniel8 (AUTHOR), Kelly, Geoffrey8 (AUTHOR), de Real, Ronaldo M.8 (AUTHOR), Lee, Brian8 (AUTHOR), Beaumont, Kristin G.9,10 (AUTHOR), Shroff, Sanjana9,10 (AUTHOR), Wang, Yuanshuo A.1,2 (AUTHOR), Wang, Ying-chih9,10 (AUTHOR), Thin, Tin Htwe11 (AUTHOR) |
| المصدر: | Cancer Cell. Sep2022, Vol. 40 Issue 9, p1027-1027. 1p. |
| مصطلحات موضوعية: | *IMMUNE checkpoint proteins, *BLADDER cancer, *T cell receptors, *HLA histocompatibility antigens, *T cells, *PROGRAMMED cell death 1 receptors, *CYTOTOXIC T cells, *URODYNAMICS |
| مستخلص: | Programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1)-blockade immunotherapies have limited efficacy in the treatment of bladder cancer. Here, we show that NKG2A associates with improved survival and responsiveness to PD-L1 blockade immunotherapy in bladder tumors that have high abundance of CD8+ T cells. In bladder tumors, NKG2A is acquired on CD8+ T cells later than PD-1 as well as other well-established immune checkpoints. NKG2A+ PD-1+ CD8+ T cells diverge from classically defined exhausted T cells through their ability to react to human leukocyte antigen (HLA) class I-deficient tumors using T cell receptor (TCR)-independent innate-like mechanisms. HLA-ABC expression by bladder tumors is progressively diminished as disease progresses, framing the importance of targeting TCR-independent anti-tumor functions. Notably, NKG2A+ CD8+ T cells are inhibited when HLA-E is expressed by tumors and partly restored upon NKG2A blockade in an HLA-E-dependent manner. Overall, our study provides a framework for subsequent clinical trials combining NKG2A blockade with other T cell-targeted immunotherapies, where tumors express higher levels of HLA-E. [Display omitted] • NKG2A associates with better survival and response to anti-PD-L1 in bladder cancer • NKG2A is upregulated after PD-1 is acquired on tumor-infiltrated CD8+ T cells • NKG2A+ CD8+ T cells react to HLA-ABC-deficient tumors with innate-like function • NKG2A blockade enhances TCR-independent cytotoxicity by CD8+ T cells Salomé et al. characterize the role of the NKG2A/HLA-E immune checkpoint axis in bladder cancer. Tumor escape mechanisms include loss of HLA-ABC expression. NKG2A+ CD8+ T cells react to advanced HLA-ABC-deficient tumors through acquired TCR-independent cytotoxicity mechanisms. NKG2A blockade further enhances their innate-like functions in the presence of HLA-E. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: | Academic Search Index |
Full Text Finder | ResultId |
1 |
|---|---|
| Header |
asx Academic Search Index 159011577 1233 6 Academic Journal academicJournal 1233.02087402344 |
| PLink |
https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&scope=site&db=asx&AN=159011577&custid=s6537998&authtype=sso |
| FullText |
Array
(
[Availability] => 0
)
Array ( [0] => Array ( [Url] => https://resolver.ebscohost.com/openurl?custid=s6537998&groupid=main&authtype=ip,guest&sid=EBSCO:asx&genre=article&issn=15356108&ISBN=&volume=40&issue=9&date=20220912&spage=1027&pages=1027-1027&title=Cancer Cell&atitle=NKG2A%20and%20HLA-E%20define%20an%20alternative%20immune%20checkpoint%20axis%20in%20bladder%20cancer.&id=DOI:10.1016/j.ccell.2022.08.005 [Name] => Full Text Finder (s6537998api) [Category] => fullText [Text] => Full Text Finder [Icon] => https://imageserver.ebscohost.com/branding/images/FTF.gif [MouseOverText] => Full Text Finder ) ) |
| Items |
Array
(
[Name] => Title
[Label] => Title
[Group] => Ti
[Data] => NKG2A and HLA-E define an alternative immune checkpoint axis in bladder cancer.
)
Array ( [Name] => Author [Label] => Authors [Group] => Au [Data] => <searchLink fieldCode="AR" term="%22Salomé%2C+Bérengère%22">Salomé, Bérengère</searchLink><relatesTo>1,2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Sfakianos%2C+John+P%2E%22">Sfakianos, John P.</searchLink><relatesTo>3</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Ranti%2C+Daniel%22">Ranti, Daniel</searchLink><relatesTo>1,2,3</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Daza%2C+Jorge%22">Daza, Jorge</searchLink><relatesTo>1,2,3</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Bieber%2C+Christine%22">Bieber, Christine</searchLink><relatesTo>1,2,3</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Charap%2C+Andrew%22">Charap, Andrew</searchLink><relatesTo>1,2,3</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Hammer%2C+Christian%22">Hammer, Christian</searchLink><relatesTo>4,5</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Banchereau%2C+Romain%22">Banchereau, Romain</searchLink><relatesTo>6</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Farkas%2C+Adam+M%2E%22">Farkas, Adam M.</searchLink><relatesTo>1,7</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Ruan%2C+Dan+Fu%22">Ruan, Dan Fu</searchLink><relatesTo>1,2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Izadmehr%2C+Sudeh%22">Izadmehr, Sudeh</searchLink><relatesTo>7</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Geanon%2C+Daniel%22">Geanon, Daniel</searchLink><relatesTo>8</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Kelly%2C+Geoffrey%22">Kelly, Geoffrey</searchLink><relatesTo>8</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22de+Real%2C+Ronaldo+M%2E%22">de Real, Ronaldo M.</searchLink><relatesTo>8</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Lee%2C+Brian%22">Lee, Brian</searchLink><relatesTo>8</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Beaumont%2C+Kristin+G%2E%22">Beaumont, Kristin G.</searchLink><relatesTo>9,10</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Shroff%2C+Sanjana%22">Shroff, Sanjana</searchLink><relatesTo>9,10</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Wang%2C+Yuanshuo+A%2E%22">Wang, Yuanshuo A.</searchLink><relatesTo>1,2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Wang%2C+Ying-chih%22">Wang, Ying-chih</searchLink><relatesTo>9,10</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Thin%2C+Tin+Htwe%22">Thin, Tin Htwe</searchLink><relatesTo>11</relatesTo> (AUTHOR) ) Array ( [Name] => TitleSource [Label] => Source [Group] => Src [Data] => <searchLink fieldCode="JN" term="%22Cancer+Cell%22">Cancer Cell</searchLink>. Sep2022, Vol. 40 Issue 9, p1027-1027. 1p. ) Array ( [Name] => Subject [Label] => Subject Terms [Group] => Su [Data] => *<searchLink fieldCode="DE" term="%22IMMUNE+checkpoint+proteins%22">IMMUNE checkpoint proteins</searchLink><br />*<searchLink fieldCode="DE" term="%22BLADDER+cancer%22">BLADDER cancer</searchLink><br />*<searchLink fieldCode="DE" term="%22T+cell+receptors%22">T cell receptors</searchLink><br />*<searchLink fieldCode="DE" term="%22HLA+histocompatibility+antigens%22">HLA histocompatibility antigens</searchLink><br />*<searchLink fieldCode="DE" term="%22T+cells%22">T cells</searchLink><br />*<searchLink fieldCode="DE" term="%22PROGRAMMED+cell+death+1+receptors%22">PROGRAMMED cell death 1 receptors</searchLink><br />*<searchLink fieldCode="DE" term="%22CYTOTOXIC+T+cells%22">CYTOTOXIC T cells</searchLink><br />*<searchLink fieldCode="DE" term="%22URODYNAMICS%22">URODYNAMICS</searchLink> ) Array ( [Name] => Abstract [Label] => Abstract [Group] => Ab [Data] => Programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1)-blockade immunotherapies have limited efficacy in the treatment of bladder cancer. Here, we show that NKG2A associates with improved survival and responsiveness to PD-L1 blockade immunotherapy in bladder tumors that have high abundance of CD8+ T cells. In bladder tumors, NKG2A is acquired on CD8+ T cells later than PD-1 as well as other well-established immune checkpoints. NKG2A+ PD-1+ CD8+ T cells diverge from classically defined exhausted T cells through their ability to react to human leukocyte antigen (HLA) class I-deficient tumors using T cell receptor (TCR)-independent innate-like mechanisms. HLA-ABC expression by bladder tumors is progressively diminished as disease progresses, framing the importance of targeting TCR-independent anti-tumor functions. Notably, NKG2A+ CD8+ T cells are inhibited when HLA-E is expressed by tumors and partly restored upon NKG2A blockade in an HLA-E-dependent manner. Overall, our study provides a framework for subsequent clinical trials combining NKG2A blockade with other T cell-targeted immunotherapies, where tumors express higher levels of HLA-E. [Display omitted] • NKG2A associates with better survival and response to anti-PD-L1 in bladder cancer • NKG2A is upregulated after PD-1 is acquired on tumor-infiltrated CD8+ T cells • NKG2A+ CD8+ T cells react to HLA-ABC-deficient tumors with innate-like function • NKG2A blockade enhances TCR-independent cytotoxicity by CD8+ T cells Salomé et al. characterize the role of the NKG2A/HLA-E immune checkpoint axis in bladder cancer. Tumor escape mechanisms include loss of HLA-ABC expression. NKG2A+ CD8+ T cells react to advanced HLA-ABC-deficient tumors through acquired TCR-independent cytotoxicity mechanisms. NKG2A blockade further enhances their innate-like functions in the presence of HLA-E. [ABSTRACT FROM AUTHOR] ) |
| RecordInfo |
Array
(
[BibEntity] => Array
(
[Identifiers] => Array
(
[0] => Array
(
[Type] => doi
[Value] => 10.1016/j.ccell.2022.08.005
)
)
[Languages] => Array
(
[0] => Array
(
[Code] => eng
[Text] => English
)
)
[PhysicalDescription] => Array
(
[Pagination] => Array
(
[PageCount] => 1
[StartPage] => 1027
)
)
[Subjects] => Array
(
[0] => Array
(
[SubjectFull] => IMMUNE checkpoint proteins
[Type] => general
)
[1] => Array
(
[SubjectFull] => BLADDER cancer
[Type] => general
)
[2] => Array
(
[SubjectFull] => T cell receptors
[Type] => general
)
[3] => Array
(
[SubjectFull] => HLA histocompatibility antigens
[Type] => general
)
[4] => Array
(
[SubjectFull] => T cells
[Type] => general
)
[5] => Array
(
[SubjectFull] => PROGRAMMED cell death 1 receptors
[Type] => general
)
[6] => Array
(
[SubjectFull] => CYTOTOXIC T cells
[Type] => general
)
[7] => Array
(
[SubjectFull] => URODYNAMICS
[Type] => general
)
)
[Titles] => Array
(
[0] => Array
(
[TitleFull] => NKG2A and HLA-E define an alternative immune checkpoint axis in bladder cancer.
[Type] => main
)
)
)
[BibRelationships] => Array
(
[HasContributorRelationships] => Array
(
[0] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Salomé, Bérengère
)
)
)
[1] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Sfakianos, John P.
)
)
)
[2] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Ranti, Daniel
)
)
)
[3] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Daza, Jorge
)
)
)
[4] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Bieber, Christine
)
)
)
[5] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Charap, Andrew
)
)
)
[6] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Hammer, Christian
)
)
)
[7] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Banchereau, Romain
)
)
)
[8] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Farkas, Adam M.
)
)
)
[9] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Ruan, Dan Fu
)
)
)
[10] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Izadmehr, Sudeh
)
)
)
[11] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Geanon, Daniel
)
)
)
[12] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Kelly, Geoffrey
)
)
)
[13] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => de Real, Ronaldo M.
)
)
)
[14] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Lee, Brian
)
)
)
[15] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Beaumont, Kristin G.
)
)
)
[16] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Shroff, Sanjana
)
)
)
[17] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Wang, Yuanshuo A.
)
)
)
[18] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Wang, Ying-chih
)
)
)
[19] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Thin, Tin Htwe
)
)
)
)
[IsPartOfRelationships] => Array
(
[0] => Array
(
[BibEntity] => Array
(
[Dates] => Array
(
[0] => Array
(
[D] => 12
[M] => 09
[Text] => Sep2022
[Type] => published
[Y] => 2022
)
)
[Identifiers] => Array
(
[0] => Array
(
[Type] => issn-print
[Value] => 15356108
)
)
[Numbering] => Array
(
[0] => Array
(
[Type] => volume
[Value] => 40
)
[1] => Array
(
[Type] => issue
[Value] => 9
)
)
[Titles] => Array
(
[0] => Array
(
[TitleFull] => Cancer Cell
[Type] => main
)
)
)
)
)
)
)
|
| IllustrationInfo |