NKG2A Blockade Potentiates CD8 T Cell Immunity Induced by Cancer Vaccines

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

doi:10.1016/j.cell.2018.10.028

Cited by 259 publications

(272 citation statements)

References 59 publications

Supporting

Mentioning

231

Contrasting

Order By: Relevance

“…In mice, loss of function of Qa-1b (equivalent to HLA-E in humans) resulting from in vivo CRISPR screening increased sensitivity of tumor cells to immune cells (80). Correlative studies in ovarian and cervical carcinomas have shown a predominant infiltration of CD8 + lymphocytes expressing NKG2A (26,81), and recently published studies indicate that an anti-NKG2A antibody can augment T cell antitumor activity (41,82). Thus, the approach described here could potentially be extended to protocols of adoptive T cell therapy of cancer.…”

Section: Discussionmentioning

confidence: 99%

Blocking expression of inhibitory receptor NKG2A overcomes tumor resistance to NK cells

Kamiya¹,

Seow²,

Wong³

et al. 2019

Journal of Clinical Investigation

256

203

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Blocking expression of inhibitory receptor NKG2A overcomes tumor resistance to NK cells

Kamiya¹,

Seow²,

Wong³

et al. 2019

Journal of Clinical Investigation

256

203

View full text Add to dashboard Cite

“…This program (ICA 25) was driven by Klrc1/NKG2A and Lag3 (Figure 3G-H), and its expression was uncoupled from that of other inhibitory receptors such as PD-1, TIM-3 or CTLA4, suggesting a potential benefit of targeting these two programs simultaneously. Indeed, dual blockade of PD-1 and LAG-3 results in robust and synergistic reinvigoration of Tex cells in cancer 52 and chronic infection 53 , while NKG2A blockade has been recently shown to potentiate CD8 T cell immunity induced by cancer vaccines 54 .…”

Section: Discussionmentioning

confidence: 99%

Projecting single-cell transcriptomics data onto a reference T cell atlas to interpret immune responses

Andreatta

Corría-Osorio

Müller³

et al. 2020

Preprint

View full text Add to dashboard Cite

Single-cell transcriptomics is a transformative technology to explore heterogeneous cell populations such as T cells, one of the most potent weapons against cancer and viral infections. Recent advances in this technology and the computational tools developed in their wake provide unique opportunities to build reference atlases that can be used to systematically compare new single-cell RNA-seq (scRNA-seq) datasets derived from different models or therapeutic conditions. We have developed ProjecTILs (https://github.com/carmonalab/ProjecTILs), a novel computational tool to project new scRNA-seq data into a reference map of T cells, allowing their direct comparison in a stable, annotated system of coordinates. ProjecTILs enables the classification of query cells into curated, discrete states, but also over a continuous space of intermediate states. We illustrate the projection of several datasets from recent publications over two novel cross-study murine T cell reference atlases: the first describing tumor-infiltrating T lymphocytes (TILs), the second characterizing acute and chronic viral infection. ProjecTILs accurately predicted the effects of multiple perturbations, including the ablation of genes controlling T cell differentiation, such as Tox, Ptpn2, miR-155 and Regnase-1, and identified novel gene programs that were altered in these cells (such as a Lag3-Klrc1 inhibitory module), revealing mechanisms of action behind these immunotherapeutic targets and opening new opportunities for the identification of novel targets. By comparing multiple samples over the same reference map, and across alternative embeddings, our method allows exploring the effect of cellular perturbations (e.g. as the result of therapy or genetic engineering) in terms of transcriptional states and altered genetic programs. *

show abstract

“…NKG2A blockade in animal model of HCV infection led to enhanced NK and CD8+ Tcell functions promoting HCV clearance [124]. NKG2A blockade combined with anti-PD-1/PD-L1 blockade was recently shown to enhance NK and T-cell anti-tumour response [125,126] in murine lymphoma tumour models and in human in vitro experiments [125]. Preliminary results of a phase II trial combining monalizumab, a humanised anti-NKG2A antibody, and cetuximab, an anti-EGFR in head and neck squamous cell carcinoma patients showed a 31% objective response rate (NCT02643550).…”

Section: Nk Cell-based Therapiesmentioning

confidence: 99%

Immune-based therapies for hepatocellular carcinoma

et al. 2020

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) is the third most frequent cause of cancer-related death. The immune-rich contexture of the HCC microenvironment makes this tumour an appealing target for immune-based therapies. Here, we discuss how the functional characteristics of the liver microenvironment can potentially be harnessed for the treatment of HCC. We will review the evidence supporting a therapeutic role for vaccines, cell-based therapies and immune-checkpoint inhibitors and discuss the potential for patient stratification in an attempt to overcome the series of failures that has characterised drug development in this disease area.

show abstract

NKG2A Blockade Potentiates CD8 T Cell Immunity Induced by Cancer Vaccines

Cited by 259 publications

References 59 publications

Blocking expression of inhibitory receptor NKG2A overcomes tumor resistance to NK cells

Blocking expression of inhibitory receptor NKG2A overcomes tumor resistance to NK cells

Projecting single-cell transcriptomics data onto a reference T cell atlas to interpret immune responses

Immune-based therapies for hepatocellular carcinoma

Contact Info

Product

Resources

About