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Stochasticity in cancer immunotherapy stems from rare but functionally-critical Spark T cells

ABSTRACT: Stochasticity in cancer immunotherapy stems from rare but functionally-critical Spark T cells

PROVIDER: PRJNA1242189 | ENA |

REPOSITORIES: ENA

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Stochasticity in cancer immunotherapy stems from rare but functionally-critical Spark T cells

Project description:Cancer immunotherapies trigger highly variable responses in patients and in genetically identical mice models. To assess the intrinsic stochasticity of these therapies, we performed thousands of well-controlled ex vivo immunoassays. We show that leukocyte responses and tumor cytotoxicity are highly variable at the macroscopic level and statistically distributed as a shifted Poisson process. Stochastic activation of a rare subpopulation of T cells (so-called Spark T cells) coupled to a paracrine IFN-γ- driven positive feedback account for this measured “noise” in immunotherapeutic reactions. We integrated these quantitative insights in a custom-designed machinelearning pipeline to analyze immune reactions with single-cell resolution; this led us to phenotypically and functionally identify the Spark T cells in murine naïve T cells, and in human T cell blasts, as prepared for adoptive T cell therapy. We then demonstrate their relevance in explaining variable outcomes in cancer immunotherapies.

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cell wall mutants -Differentially expressed genes in stems of Arabidopsis deficient in monolignol export and in stems of Arabidopsis plants expressing a hydroxycinnamoyl-CoA hydratase/lyase

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