NKG2A Blockade Potentiates CD8 T Cell Immunity Induced by Cancer Vaccines

被引：282

作者：

van Montfoort, Nadine ^{[1
]}

Borst, Linda ^{[1
]}

Korrer, Michael J. ^{[2
]}

Sluijter, Marjolein ^{[1
]}

Marijt, Koen A. ^{[1
]}

Santegoets, Saskia J. ^{[1
]}

van Ham, Vanessa J. ^{[1
]}

Ehsan, Ilina ^{[1
]}

Charoentong, Pornpimol ^{[3
]}

Andre, Pascale ^{[4
]}

Wagtmann, Nicolai ^{[4
,6
]}

Welters, Marij J. P. ^{[1
]}

Kim, Young J. ^{[2
]}

Piersma, Sytse J. ^{[5
]}

van der Burg, Sjoerd H. ^{[1
]}

van Hall, Thorbald ^{[1
]}

机构：

[1] Leiden Univ, Dept Med Oncol, Med Ctr, NL-2333 ZA Leiden, Netherlands

[2] Vanderbilt Univ, Med Ctr, Dept Otolaryngol, Nashville, TN 37232 USA

[3] Univ Hosp Heidelberg, Natl Ctr Tumor Dis, Dept Med Oncol, D-69120 Heidelberg, Germany

[4] Innate Pharma, F-13276 Marseille 09, France

[5] Washington Univ, Sch Med, Dept Med, Div Rheumatol, St Louis, MO 63110 USA

[6] Dragonfly Therapeut, Waltham, MA 02451 USA

来源：

CELL | 2018年 / 175卷 / 07期

关键词：

VULVAR INTRAEPITHELIAL NEOPLASIA; RECEPTORS CD94/NKG2A; INHIBITORY RECEPTORS; HUMAN-PAPILLOMAVIRUS; CHECKPOINT BLOCKADE; PEPTIDE VACCINE; IFN-GAMMA; EXPRESSION; LYMPHOCYTES; SURVIVAL;

D O I：

10.1016/j.cell.2018.10.028

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Tumor-infiltrating CD8 T cells were found to frequently express the inhibitory receptor NKG2A, particularly in immune-reactive environments and after therapeutic cancer vaccination. High-dimensional cluster analysis demonstrated that NKG2A marks a unique immune effector subset preferentially co-expressing the tissue-resident CD103 molecule, but not immune checkpoint inhibitors. To examine whether NKG2A represented an adaptive resistance mechanism to cancer vaccination, we blocked the receptor with an antibody and knocked out its ligand Qa-1(b), the conserved ortholog of HLA-E, in four mouse tumor models. The impact of therapeutic vaccines was greatly potentiated by disruption of the NKG2A/Qa-1(b) axis even in a PD-1 refractory mouse model. NKG2A blockade therapy operated through CD8 T cells, but not NK cells. These findings indicate that NKG2A-blocking antibodies might improve clinical responses to therapeutic cancer vaccines.

引用

页码：1744 / +

页数：27

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