Prior Chemotherapy Deteriorates T Cell Quality for CAR T Cell Therapy in B-Cell Non-Hodgkin’s Lymphoma
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PROVIDER: PRJNA1153933 | ENA |
REPOSITORIES: ENA
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Project description:Prior chemotherapy deteriorates T-cell quality for CAR T-cell therapy in B-cell non-Hodgkin’s lymphoma
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Project description:Chimeric antigen receptor (CAR) T cell therapy depends on T cells that are genetically modified to recognize and attack cancer cells. Their effectiveness thus hinges on the functionality of a patient’s own T cells. However, CAR T cell therapy is currently only approved for advanced cancers after at least one line of chemotherapy. To evaluate the potential negative effects of prior exposure to chemotherapy on T cell functionality we studied T cells of two B cell Non-Hodgkin’s lymphoma (B-NHL) patient cohorts, one collected before treatment (pre-therapy) and the other after one or more (median 3) lines of chemotherapy (post-therapy). Leveraging advanced multi-parameter flow cytometry and single-cell RNA sequencing (scRNAseq), we elucidated significant modifications in T cell subsets and their transcriptional profiles post-therapy. Our analysis revealed a discernible shift towards phenotypically more differentiated T cells and an upregulation of markers indicative of T cell exhaustion. Additionally, scRNAseq and DNA methylation analyses revealed gene expression and epigenetic changes associated with diminished functionality in post-therapy T cells. Cytotoxicity assays demonstrated superior killing efficacy of CAR T cells derived from treatment-naïve patients compared to those with chemotherapy history. These findings corroborate that employing T cells collected prior to frontline chemotherapy could enhance the effectiveness of CAR T cell therapy and improve patient outcomes.
2025-04-10 | GSE275947 | GEO
Project description:Immunotherapies, such as CAR T cell therapy, depend on T cells that are genetically modified to recognize and attack cancer cells. Their effectiveness thus hinges on the quality of a patient’s own T cells. We studied blood samples from B-NHL patients collected both before any treatment (pre-therapy) and following at least two lines of chemotherapy (post-therapy) to evaluate the potential negative effects of prior exposure to chemotherapy on T cell quality. Utilizing advanced multi-parameter flow cytometry and single-cell RNA sequencing (scRNAseq), we discovered notable alterations in T cell composition and gene expression after therapy, such as increasingly differentiated phenotypes and elevated expression of exhaustion markers. Additionally, scRNAseq and DNA methylation analyses revealed gene expression and epigenetic changes associated with diminished T cell function in post-therapy samples. In vitro cytotoxicity studies demonstrated superior killing efficacy of CAR T cells derived from T cells of treatment-naïve patients compared to T cells of patients with treatment history. These findings corroborate that using T cells collected prior to chemotherapy exposure could enhance the effectiveness of CAR T cell therapies and offer new strategies for improving patient outcomes in B-NHL treatment.
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Project description:Lymphomas are classified according to the World Health Organization (WHO) classification which defines subtypes on the basis of clinical, morphological, immunophenotypic, molecular and cytogenetic criteria. Using this model, 8 of 9 of the validation samples were classified successfully. This pilot study demonstrates that such a microarray tool may be a promising diagnostic approach for small B-cell non-Hodgkin’s lymphoma. Keywords: Small B-Cell non-Hodgkin’s Lymphoma, Low Density DNA Microarray, Diagnosis
2009-03-25 | GSE11635 | GEO
Project description:Gene expression profiles were performed from CD3+ T cells isolated from peripheral blood samples of untreated patients with cHL versus 2 control groups consisting of healthy donors and patients with sarcoidosis. Keywords = Hodgkin’s Lymphoma Keywords = T cell Keywords = immune regulation Keywords: repeat sample
2005-07-13 | GSE2657 | GEO
Project description:Lymphomas are classified according to the World Health Organization (WHO) classification which defines subtypes on the basis of clinical, morphological, immunophenotypic, molecular and cytogenetic criteria. Using this model, 8 of 9 of the validation samples were classified successfully. This pilot study demonstrates that such a microarray tool may be a promising diagnostic approach for small B-cell non-Hodgkin’s lymphoma. Keywords: Small B-Cell non-Hodgkin’s Lymphoma, Low Density DNA Microarray, Diagnosis Fresh-frozen tumor biopsies performed before treatment and clinical data were obtained retrospectively from 68 patients in five different institutions after lab investigations involving cytology, immunohistochemistry, cytogenetics (conventional cytogenetics and fluorescent in situ hybridization [FISH]), and/or molecular analysis. The samples were then classified unanimously by a panel of five pathologists as one of the 4 subtypes: 17 B-CLL, 14 MZL, 23 FL and 14 MCL. The immunohistochemical criteria used for identifying the 4 subtypes of SBCL were: CD20+/-, CD5+, CD23+ for B-CLL; CD20+, CD5+, CD23-, Cyclin D1+ for MCL; CD20+, CD10+, Bcl2+ for FL; CD20+, CD5-, CD10- for S-MZL. 28 samples were rejected for technical issues with RNA. The remaining 40 samples include the 4 different subtypes with this following distribution: Follicular Lymphoma/FL (n=15), Mantle Cell Lymphoma/MCL (n=7), B-Chronic Lymphocytic Leukemia/B-CLL (n=6) and Splenic Marginal Zone Lymphoma/S-MZL (n=12). The expression profile of 107 genes was evaluated in these 40 samples defined as a training set. Replicates were performed for samples of sufficient quantity, and a total of 79 gene expression profiles, comprised of 12 samples in triplicate, 15 samples in duplicate and 13 samples evaluated singly, were then analyzed. A second group of 13 patients was defined as test set and used to validate the gene signatures highlighted from the training set analysis. These patients were selected by a pathologist independent from the first analysis and include 4 FL, 3 B-CLL, 5 MCL and 1 S-MZL. Four samples were rejected for technical issues with RNA. The remaining 9 samples include the 4 different subtypes: 2 FL, 3 B-CLL, 3 MCL and 1 S-MZL. A total of 13 gene expression profiles were analyzed (4 samples evaluated in duplicate and 5 samples investigated singly).
2009-03-24 | E-GEOD-11635 | biostudies-arrayexpress
Project description:Luminal B breast carcinoma samples were taken prior to chemotherapy in order to identify epigenomic profiles predictive of neoadjuvant chemotherapy efficacy
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Project description:Triple negative breast carcinoma samples were taken prior to chemotherapy in order to identify epigenomic profiles predictive of neoadjuvant chemotherapy efficacy
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Project description:Gene expression profiles of malignant carcinomas surgically removed from ovarian cancer patients pre-treated with chemotherapy (neo-adjuvant) prior to surgery group into two distinct clusters. One group clusters with carcinomas from patients not pre-treated with chemotherapy prior to surgery (C-L) while the other clusters with non-malignant adenomas (A-L). Although the C-L cluster is preferentially associated with p53 loss-of-function (LOF) mutations, the C-L cluster cancer patients display a more favorable clinical response to chemotherapy as evidenced by enhanced long-term survivorships. Experiment Overall Design: A set of 43 ovarian tumors was obtained from the Ovarian Cancer Institute (Atlanta). Tissue was collected at the time of surgery and preserved in RNAlater (Ambion, Austin, TX) within one minute of collection. Labeled probe was hybridized to the Affymetrix HG-U95Av2 arrays.
2008-11-22 | E-GEOD-7463 | biostudies-arrayexpress