The DOI matches its Crossref record; 60 of the 60 references it cites were found in a registry or an index.
LAG-3 and PD-1 synergize on CD8+ T cells to drive T cell exhaustion and hinder autocrine IFN-γ-dependent anti-tumor immunity
Open accessAbstract
SUMMARY Overcoming immune-mediated resistance to PD1 blockade remains a major clinical challenge. Enhanced efficacy has been demonstrated in melanoma patients with combined nivolumab (anti-PD1) and relatlimab (anti-LAG3) treatment, the first in its class to be FDA-approved. However, how these two inhibitory receptors synergize to hinder anti-tumor immunity remains unknown. Here, we show that PD1/LAG3-deficient CD8+ T cells, in contrast to CD8+ T cells lacking either receptor, mediate enhanced tumor clearance and long-term survival in mouse models of melanoma. PD1/LAG3-deficient CD8+ T cells were transcriptionally distinct, with broad TCR clonality and enrichment of effector-like and interferon-responsive genes, resulting in enhanced IFNγ release indicative of functionality. LAG3 and PD1 combined to drive T cell exhaustion, playing a dominant role in modulating TOX expression. Mechanistically, autocrine, cell-intrinsic IFNγ signaling was required for PD1/LAG3-deficient CD8+ T cells to enhance anti-tumor immunity, providing insight into how combinatorial targeting of LAG3 and PD1 enhances efficacy.
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Cites
PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer
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Comprehensive Integration of Single-Cell Data
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Adverse Renal Effects of Immune Checkpoint Inhibitors: A Narrative Review
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Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma
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Metadata
- Authors
- Andrews, L. P., Butler, S. C., Cui, J., Cillo, A. R., Cardello, C., Liu, C., Brunazzi, E. A., Baessler, A., Xie, B., Kunning, S. R., Ngiow, S. F., Huang, Y. J., Manne, S., Sharpe, A. H., Delgoffe, G. M., Wherry, E. J., Kirkwood, J. M., Bruno, T. C., Workman, C. J., & Vignali, D. A. A.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2024-08
- Volume
- 187
- Issue
- 16
- Pages
- 4355-4372.e22
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W4401420347
- Cited by
- 279
- References
- 60
- FWCI
- 42.82
- Type
- journal article
- Language
- en
- Open access
- bronze
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- CoChat. (2026). Citation check: LAG-3 and PD-1 synergize on CD8+ T cells to drive T cell exhaustion and hinder autocrine IFN-γ-dependent anti-tumor immunity. https://app.cochat.ai/papers/10.1016/j.cell.2024.07.016
- The paper
- Andrews, L. P., Butler, S. C., Cui, J., Cillo, A. R., Cardello, C., Liu, C., Brunazzi, E. A., Baessler, A., Xie, B., Kunning, S. R., Ngiow, S. F., Huang, Y. J., Manne, S., Sharpe, A. H., Delgoffe, G. M., Wherry, E. J., Kirkwood, J. M., Bruno, T. C., Workman, C. J., & Vignali, D. A. A. (2024). LAG-3 and PD-1 synergize on CD8+ T cells to drive T cell exhaustion and hinder autocrine IFN-γ-dependent anti-tumor immunity. Cell. https://doi.org/10.1016/j.cell.2024.07.016
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
