2. Academic Validation
  3. NKG2A Blockade Potentiates CD8 T Cell Immunity Induced by Cancer Vaccines

NKG2A Blockade Potentiates CD8 T Cell Immunity Induced by Cancer Vaccines

  • Cell. 2018 Dec 13;175(7):1744-1755.e15. doi: 10.1016/j.cell.2018.10.028.
Nadine van Montfoort 1,  Linda Borst 1,  Michael J Korrer 2,  Marjolein Sluijter 1,  Koen A Marijt 1,  Saskia J Santegoets 1,  Vanessa J van Ham 1,  Ilina Ehsan 1,  Pornpimol Charoentong 3,  Pascale André 4,  Nicolai Wagtmann 4,  Marij J P Welters 1,  Young J Kim 2,  Sytse J Piersma 5,  Sjoerd H van der Burg 1,  Thorbald van Hall 6
Affiliations

Affiliations

  • 1 Department of Medical Oncology, Leiden University Medical Center, 2333 ZA, Leiden, the Netherlands.
  • 2 Department of Otolaryngology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • 3 Department of Medical Oncology, National Center for Tumor diseases, University Hospital Heidelberg, 69120 Heidelberg, Germany.
  • 4 Innate Pharma, 13276 Marseille Cedex 09, France.
  • 5 Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • 6 Department of Medical Oncology, Leiden University Medical Center, 2333 ZA, Leiden, the Netherlands. Electronic address: t.van_hall@lumc.nl.
PMID: 30503208 DOI: 10.1016/j.cell.2018.10.028
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.

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