Blockade of LAG-3 and PD-1 leads to co-expression of cytotoxic and exhaustion gene modules in CD8+ T cells to promote antitumor immunity

Relatlimab (rela; anti-LAG-3) plus nivolumab (nivo; anti-PD-1) is safe and effective for treatment of advanced melanoma. We designed a trial (NCT03743766) where advanced melanoma patients received rela, nivo, or rela+nivo to interrogate the immunologic mechanisms of rela+nivo. Analysis of biospecime...

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Veröffentlicht in:	Cell 2024-08, Vol.187 (16), p.4373-4388.e15
Hauptverfasser:	Cillo, Anthony R., Cardello, Carly, Shan, Feng, Karapetyan, Lilit, Kunning, Sheryl, Sander, Cindy, Rush, Elizabeth, Karunamurthy, Arivarasan, Massa, Ryan C., Rohatgi, Anjali, Workman, Creg J., Kirkwood, John M., Bruno, Tullia C., Vignali, Dario A.A.
Format:	Artikel
Sprache:	eng
Schlagworte:	advanced melanoma Antigens, CD - genetics Antigens, CD - metabolism antitumor immunity Basic-Leucine Zipper Transcription Factors - genetics Basic-Leucine Zipper Transcription Factors - metabolism CD8+ T cell transcriptional profiles CD8-Positive T-Lymphocytes - immunology CD8-Positive T-Lymphocytes - metabolism Cell Differentiation checkpoint blockade combination immunotherapy Cytotoxicity, Immunologic High Mobility Group Proteins Humans Immune Checkpoint Inhibitors - pharmacology Immune Checkpoint Inhibitors - therapeutic use inhibitory receptors LAG-3 Lymphocyte Activation Gene 3 Protein - antagonists & inhibitors Melanoma - drug therapy Melanoma - genetics Melanoma - immunology Nivolumab - pharmacology Nivolumab - therapeutic use PD-1 Positive Regulatory Domain I-Binding Factor 1 - genetics Positive Regulatory Domain I-Binding Factor 1 - metabolism Programmed Cell Death 1 Receptor - antagonists & inhibitors Signal Transduction T cell exhaustion
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