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The immune system profoundly restricts intratumor genetic heterogeneity

Abstract : Tumors develop under the selective pressure of the immune system. However, it remains critical to establish how the immune system affects the clonal heterogeneity of tumors that often display cell-to-cell variation in genetic alterations and antigenic expression. To address these questions, we introduced a multicolor barcoding strategy to study the growth of a MYC-driven B cell lymphoma harboring a large degree of intratumor genetic diversity. Using intravital imaging, we visualized that lymphoma subclones grow as patches of sessile cells in the bone marrow, creating a spatially compartmentalized architecture for tumor diversity. Using multicolor barcoding and whole-exome sequencing, we demonstrated that immune responses strongly restrict intratumor genomic diversity and favor clonal dominance, a process mediated by the selective elimination of more immunogenic cells and amplified by epitope spreading. Anti-PD-1 treatment also narrowed intratumor diversity. Our results provide direct evidence that immune pressure shapes the level of intratumor genetic heterogeneity and have important implications for the design of therapeutic strategies.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-01939341
Contributor : Bérengère Hugot <>
Submitted on : Thursday, November 29, 2018 - 1:31:52 PM
Last modification on : Thursday, October 15, 2020 - 2:42:03 PM

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Idan Milo, Marie Bedora-Faure, Zacarias Garcia, Ronan Thibaut, Leïla Perié, et al.. The immune system profoundly restricts intratumor genetic heterogeneity. Science Immunology, American Association for the Advancement of Science, 2018, 3 (29), pp.eaat1435. ⟨10.1126/sciimmunol.aat1435⟩. ⟨pasteur-01939341⟩

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