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Immune cell networks in tumors predict response to an immune cell therapy for melanoma

David Barras, Ludwig Cancer Research Lausanne
David Barras
Eleonora Ghisoni, Ludwig Cancer Research Lausanne
Eleonora Ghisoni
Johanna Chiffelle, Ludwig Cancer Research Lausanne
Johanna Chiffelle
Denarda Dangaj Laniti, Ludwig Cancer Research Lausanne
Denarda Dangaj Laniti
George Coukos, Ludwig Cancer Research Lausanne
George Coukos

Researchers led by Ludwig Lausanne’s David Barras, Eleonora Ghisoni, Johanna Chiffelle, Denarda Dangaj Laniti and Branch Director George Coukos reported in a Science Immunology paper in February that pre-existing immune cell networks in tumors predict whether patients with advanced melanoma are likely to respond to a personalized immunotherapy known as TIL-ACT. In TIL-ACT, tumor infiltrating lymphocytes (TILs) that kill cancer cells are isolated from tumors, grown in the lab and infused into patients for therapy. The researchers collected tumor samples from patients enrolled in a small trial at Lausanne before TIL-ACT therapy started and then at various time points thereafter. Tumors that responded best to TIL-ACT were those that were most riddled with mutations and harbored killer T cells in states with a potential for intense anti-tumor activation. The immune cell networks the researchers identified consist of killer T cells in close association with activated dendritic cells and macrophages. Successful TIL-ACT therapy further expanded and activated these immune cell networks. Macrophages additionally expressed a molecule named CXCL9 that likely bolsters stimulatory interactions with T cells. The study described biomarkers that, with further vetting, could help clinicians select patients for TIL-ACT—which was approved for treating melanoma for the first time in the U.S. in February. The findings could also inform interventions to broaden the pool of patients who benefit from the therapy.

Response to tumor-infiltrating lymphocyte adoptive therapy is associated with preexisting CD8+ T-myeloid cell networks in melanoma
Science Immunology, 2024 February 2

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