NKG2A Blockade Potentiates CD8 T Cell Immunity Induced by Cancer Vaccines

Nadine van Montfoort; Linda Borst; Michael J. Korrer; Marjolein Sluijter; Koen A. Marijt; Saskia J. Santegoets; Vanessa J. van Ham; Ilina Ehsan; Pornpimol Charoentong; Pascale André; Nicolai Wagtmann; Marij J.P. Welters; Young J. Kim; Sytse J. Piersma; Sjoerd H. van der Burg; Thorbald van Hall

doi:10.1016/j.cell.2018.10.028

NKG2A Blockade Potentiates CD8 T Cell Immunity Induced by Cancer Vaccines

Nadine van Montfoort
, Linda Borst
, Michael J. Korrer
, Marjolein Sluijter
, Koen A. Marijt
, Saskia J. Santegoets
, Vanessa J. van Ham
, Ilina Ehsan
, Pornpimol Charoentong
, Pascale André
, Nicolai Wagtmann
, Marij J.P. Welters
, Young J. Kim
, Sytse J. Piersma
, Sjoerd H. van der Burg
, Thorbald van Hall

Research output: Contribution to journal › Article › peer-review

287 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	1744-1755.e15
Journal	Cell
Volume	175
Issue number	7
DOIs	https://doi.org/10.1016/j.cell.2018.10.028
State	Published - Dec 13 2018

Keywords

CD8 T cells
HLA-E
IFN-γ
NKG2A
Qa-1
acquired resistance
cancer vaccines
immune checkpoints
mouse tumor models
natural killer cells

Access to Document

10.1016/j.cell.2018.10.028

Cite this

van Montfoort, N., Borst, L., Korrer, M. J., Sluijter, M., Marijt, K. A., Santegoets, S. J., van Ham, V. J., Ehsan, I., Charoentong, P., André, P., Wagtmann, N., Welters, M. J. P., Kim, Y. J., Piersma, S. J., van der Burg, S. H., & van Hall, T. (2018). NKG2A Blockade Potentiates CD8 T Cell Immunity Induced by Cancer Vaccines. Cell, 175(7), 1744-1755.e15. https://doi.org/10.1016/j.cell.2018.10.028

@article{c0cf80e81d74459d8cd0eaddd54954b1,

title = "NKG2A Blockade Potentiates CD8 T Cell Immunity Induced by Cancer Vaccines",

abstract = "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-1b, 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-1b 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.",

keywords = "CD8 T cells, HLA-E, IFN-γ, NKG2A, Qa-1, acquired resistance, cancer vaccines, immune checkpoints, mouse tumor models, natural killer cells",

author = "\{van Montfoort\}, Nadine and Linda Borst and Korrer, \{Michael J.\} and Marjolein Sluijter and Marijt, \{Koen A.\} and Santegoets, \{Saskia J.\} and \{van Ham\}, \{Vanessa J.\} and Ilina Ehsan and Pornpimol Charoentong and Pascale Andr{\'e} and Nicolai Wagtmann and Welters, \{Marij J.P.\} and Kim, \{Young J.\} and Piersma, \{Sytse J.\} and \{van der Burg\}, \{Sjoerd H.\} and \{van Hall\}, Thorbald",

note = "Publisher Copyright: {\textcopyright} 2018 Elsevier Inc.",

year = "2018",

month = dec,

day = "13",

doi = "10.1016/j.cell.2018.10.028",

language = "English",

volume = "175",

pages = "1744--1755.e15",

journal = "Cell",

issn = "0092-8674",

number = "7",

}

van Montfoort, N, Borst, L, Korrer, MJ, Sluijter, M, Marijt, KA, Santegoets, SJ, van Ham, VJ, Ehsan, I, Charoentong, P, André, P, Wagtmann, N, Welters, MJP, Kim, YJ, Piersma, SJ, van der Burg, SH & van Hall, T 2018, 'NKG2A Blockade Potentiates CD8 T Cell Immunity Induced by Cancer Vaccines', Cell, vol. 175, no. 7, pp. 1744-1755.e15. https://doi.org/10.1016/j.cell.2018.10.028

TY - JOUR

T1 - NKG2A Blockade Potentiates CD8 T Cell Immunity Induced by Cancer Vaccines

AU - van Montfoort, Nadine

AU - Borst, Linda

AU - Korrer, Michael J.

AU - Sluijter, Marjolein

AU - Marijt, Koen A.

AU - Santegoets, Saskia J.

AU - van Ham, Vanessa J.

AU - Ehsan, Ilina

AU - Charoentong, Pornpimol

AU - André, Pascale

AU - Wagtmann, Nicolai

AU - Welters, Marij J.P.

AU - Kim, Young J.

AU - Piersma, Sytse J.

AU - van der Burg, Sjoerd H.

AU - van Hall, Thorbald

PY - 2018/12/13

Y1 - 2018/12/13

N2 - 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-1b, 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-1b 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.

AB - 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-1b, 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-1b 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.

KW - CD8 T cells

KW - HLA-E

KW - IFN-γ

KW - NKG2A

KW - Qa-1

KW - acquired resistance

KW - cancer vaccines

KW - immune checkpoints

KW - mouse tumor models

KW - natural killer cells

UR - https://www.scopus.com/pages/publications/85058015117

U2 - 10.1016/j.cell.2018.10.028

DO - 10.1016/j.cell.2018.10.028

M3 - Article

C2 - 30503208

AN - SCOPUS:85058015117

SN - 0092-8674

VL - 175

SP - 1744-1755.e15

JO - Cell

JF - Cell

IS - 7

ER -

NKG2A Blockade Potentiates CD8 T Cell Immunity Induced by Cancer Vaccines

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this