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The Tumor Microenvironment and Inflammation Influence toxicity in patients with Large B Cell Lymphoma Treated with Axicabtagene Ciloleucel [Nanostring]

ABSTRACT: The Tumor Microenvironment and Inflammation Influence toxicity in patients with Large B Cell Lymphoma Treated with Axicabtagene Ciloleucel [Nanostring]

PROVIDER: PRJNA642656 | ENA |

REPOSITORIES: ENA

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The Tumor Microenvironment and Inflammation Influence toxicity in patients with Large B Cell Lymphoma Treated with Axicabtagene Ciloleucel

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The Tumor Microenvironment and Inflammation Influence toxicity in patients with Large B Cell Lymphoma Treated with Axicabtagene Ciloleucel [RNA-Seq]

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The Tumor Microenvironment and Inflammation Influence toxicity in patients with Large B Cell Lymphoma Treated with Axicabtagene Ciloleucel [Nanostring]

Project description:Tumor biopsies were taken within one month prior to CAR T infusion for evaluation of gene expression. Baseline tumor gene expression was compared between patients who went on to have severe (grade 3 or higher) neurotoxicity vs. those with non-severe neurotoxicity (grade 0 - 2).

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The Tumor Microenvironment and Inflammation Influence toxicity in patients with Large B Cell Lymphoma Treated with Axicabtagene Ciloleucel [RNA-Seq]

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The Tumor Microenvironment and Inflammation Influence toxicity in patients with Large B Cell Lymphoma Treated with Axicabtagene Ciloleucel

Project description:This SuperSeries is composed of the SubSeries listed below.

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Project description:Single-cell dynamics of breakthrough toxicities following anakinra prophylaxis for axicabtagene ciloleucel treatment in lymphoma

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Two-Stage CAR T-Cell Differentiation in Patients with Large B-Cell Lymphoma

Project description:To investigate the CAR T-cell differentiation in vivo, we performed single-cell, multi-omics analyses of CD28-costimulated CAR T cells from patients with DLBCL who were successfully treated with axicabtagene ciloleucel. Our data shows that CAR T cells undergo two distinct stages of post-infusion clonal expansion.

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Tumor Microenvironment Composition and Severe Cytokine Release Syndrome (CRS) Influence Toxicity in Patients with Large B-Cell Lymphoma Treated with Axicabtagene Ciloleucel.

Project description:PurposeOne of the challenges of adoptive T-cell therapy is the development of immune-mediated toxicities including cytokine release syndrome (CRS) and neurotoxicity (NT). We aimed to identify factors that place patients at high risk of severe toxicity or treatment-related death in a cohort of 75 patients with large B-cell lymphoma treated with a standard of care CD19 targeted CAR T-cell product (axicabtagene ciloleucel).Experimental designSerum cytokine and catecholamine levels were measured prior to lymphodepleting chemotherapy, on the day of CAR T infusion and daily thereafter while patients remained hospitalized. Tumor biopsies were taken within 1 month prior to CAR T infusion for evaluation of gene expression.ResultsWe identified an association between pretreatment levels of IL6 and life-threatening CRS and NT. Because the risk of toxicity was related to pretreatment factors, we hypothesized that the tumor microenvironment (TME) may influence CAR T-cell toxicity. In pretreatment patient tumor biopsies, gene expression of myeloid markers was associated with higher toxicity.ConclusionsThese results suggest that a proinflammatory state and an unfavorable TME preemptively put patients at risk for toxicity after CAR T-cell therapy. Tailoring toxicity management strategies to patient risk may reduce morbidity and mortality.

| S-EPMC7501265 | biostudies-literature

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