Asset Details
Do you wish to reserve the book?
Tumor immune contexture is a determinant of anti-CD19 CAR T cell efficacy in large B cell lymphoma
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Tumor immune contexture is a determinant of anti-CD19 CAR T cell efficacy in large B cell lymphoma
Do you wish to request the book?
Tumor immune contexture is a determinant of anti-CD19 CAR T cell efficacy in large B cell lymphoma
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Tumor immune contexture is a determinant of anti-CD19 CAR T cell efficacy in large B cell lymphoma
2022
Overview
Axicabtagene ciloleucel (axi-cel) is an anti-CD19 chimeric antigen receptor (CAR) T cell therapy approved for relapsed/refractory large B cell lymphoma (LBCL) and has treatment with similar efficacy across conventional LBCL subtypes. Toward patient stratification, we assessed whether tumor immune contexture influenced clinical outcomes after axi-cel. We evaluated the tumor microenvironment (TME) of 135 pre-treatment and post-treatment tumor biopsies taken from 51 patients in the ZUMA-1 phase 2 trial. We uncovered dynamic patterns that occurred within 2 weeks after axi-cel. The biological associations among Immunoscore (quantification of tumor-infiltrating T cell density), Immunosign 21 (expression of pre-defined immune gene panel) and cell subsets were validated in three independent LBCL datasets. In the ZUMA-1 trial samples, clinical response and overall survival were associated with pre-treatment immune contexture as characterized by Immunoscore and Immunosign 21. Circulating CAR T cell levels were associated with post-treatment TME T cell exhaustion. TME enriched for chemokines (CCL5 and CCL22), γ-chain receptor cytokines (IL-15, IL-7 and IL-21) and interferon-regulated molecules were associated with T cell infiltration and markers of activity. Finally, high density of regulatory T cells in pre-treatment TME associated with reduced axi-cel–related neurologic toxicity. These findings advance the understanding of LBCL TME characteristics associated with clinical responses to anti-CD19 CAR T cell therapy and could foster biomarker development and treatment optimization for patients with LBCL.
Analysis of tumor biopsies from the pivotal phase 1/2 ZUMA-1 trial identifies pre-treatment T cell–related characteristics that are associated with clinical response and neurologic toxicity after anti-CD19 CAR T cell therapy in patients with large B cell lymphoma.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ Antigens
/ Biomedical and Life Sciences
/ Biopsy
/ Density
/ Humans
/ Immunotherapy, Adoptive - adverse effects
/ Interferons - therapeutic use
/ Interleukin-7 - therapeutic use
/ Lymphoma
/ Lymphoma, Large B-Cell, Diffuse - therapy
/ Patients
/ Receptors, Chimeric Antigen - genetics
/ Receptors, Chimeric Antigen - therapeutic use
/ Therapy
/ Toxicity
/ Tumors
