ScRNA and TCR-Seq of peripheral blood mononuclear cells (PBMC) from r/r classical Hodgkin Lymphoma patients under anti-PD1 therapy.
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE290026 | GEO | 2025/02/24
REPOSITORIES: GEO
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Project description:Classical Hodgkin lymphoma (cHL) is a highly curable disease, with about 80% of patients cured using standard first-line chemotherapy. However, outcomes for relapsed/refractory patients re-main unfavorable and there is a critical lack of predictive biomarkers for early identification of these patients who may benefit from new therapeutic strategies. Here we evaluated the dynamic expression of 571 immune-related genes in a cohort of 42 cHL using NanoString technology. We identified a 19-genes immune signature predictive of relapse at the time of diagnosis, which was found to be strongly dependent on histological subtype. Moreover, comparative analyses be-tween paired diagnostic/relapsed biopsies of nodular sclerosis cHL showed 134 differentially expressed genes, highlighting an immune contexture shift at relapse not found in the mixed-cellularity subtype. Overall, these results strongly suggest that the predictive value of immune signature in cHL is influenced by histological subtype, a criterion that should be con-sidered when assessing new immunotherapy strategies.
2022-10-10 | GSE212902 | GEO
Project description:scRNA and TCR-Seq of peripheral blood mononuclear cells (PBMC) from r/r classical Hodgkin Lymphoma patients under anti-PD1 therapy.
| PRJNA1225759 | ENA
Project description:We successfully developed a two-in-one approach to generate non-viral genome specific targeted CAR T cells through CRISPR/Cas9. In the adoptive therapy for relapsed/refractory aggressive B-cell non-Hodgkin lymphoma, we observed durable responses without serious adverse events and complete remission in patients treated with PD1 knockin CAR T cells. Here we applied single-cell sequencing to analyze the characteristcis of infusion products and T cells after administration.
2022-06-20 | GSE166352 | GEO
Project description:BACKGROUND: Classical Hodgkin lymphoma is dominated by the nonneoplastic microenvironment, while the neoplastic Hodgkin-Reed-Sternberg cells compose only a minority of cells in the lymphoma tissue. Both, the Hodgkin-Reed-Sternberg cells due to their expression of CD30 and PD-L1 and the microenvironment with abundant T-cells and expression of PD1 are specifically targeted by new treatment concepts. AIM: We aimed to understand the dynamics of therapeutic targets in patients treated with conventional chemotherapy. METHODS: We analyzed sequential biopsy specimens obtained at diagnosis and at relapse from the same patient for morphology, immunophenotype and microenvironmental components. RESULTS: The morphological subtype changed between primary and relapse biopsy in 20% of cases. The immunophenotype was stable with respect to CD30, CD3 and LMP1 but variable with respect to CD15 and CD20 expression. Gene expression revealed 8 up- and 20 down-regulated genes at relapse (p≤0.05) with a consistent logarithmic fold change direction in at least 75% of all cases. For PD1, we found discrepant results between gene expression analysis (decrease at relapse) and number of PD1 positive cells assessed by immunohistochemistry (unchanged at relapse). PD-L1 in the neoplastic cells appeared unchanged between primary diagnosis and relapse. CONCLUSION: The expression of the therapeutic targets CD30, PD1 and PD-L1 can reliably be assessed in tumor specimen at first diagnosis and are unchanged under conventional chemotherapy. We used digital multiplexed gene expression (DMGE) with FFPE derived RNA to analyze sequential biopsy specimens obtained at diagnosis and at relapse from the same patient for morphology, immunophenotype and microenvironmental components.
2019-06-24 | GSE125651 | GEO
Project description:Classical Hodgkin lymphoma (cHL) is one of the most prevalent lymphomas with a unique cell composition compared to other lymphoma entities. Rare, malignant Hodgkin and Reed-Sternberg (HRS) cells embedded with an extensive but ineffective immune infiltration were previously characterized by a large number of genetic and epigenetic alterations. Recently, microRNA profiling studies highlighted the importance of small non-coding RNA in cHL. This review summarizes available literature data and provides a detailed comparison of four studies where cHL cell lines and microdissected HRS cells were used. Several microRNAs were found to be consistently up- (let-7-f, mir-9, mir-21, mir-23a, mir-27a, mir-155, and mir-196a) or downregulated (mir-138 and mir-150) in cHL. These deregulated microRNAs are involved in the processes crucial for cHL pathogenesis, such as impaired B cell development (mir-9, mir-150, and mir-155), NFκB hyperactivation (mir-155 and mir-196a), and immune evasion (mir-138). Therefore, the deregulation of microRNA expression can be considered a complementary mechanism to genetic alterations promoting lymphomagenesis. Moreover, the expression of let-7f, mir-9 and mir-27a is specific for cHL and can serve as a biomarker to distinguish this lymphoma from other B cell lymphomas. However, additional in-depth and high throughput analysis of microRNA expression in HRS cells is necessary to decipher the complete picture of microRNA in cHL.
| S-EPMC8032569 | biostudies-literature
Project description:Recent success in cancer immunotherapy has come from the blockade of inhibitory receptors on T cells, such as programmed cell death-1, which can induce a state of T cell exhaustion upon constant antigen stimulation. Understanding miRNA regulation of PD1 can be useful to discover miRNAs for use in therapy or as prognostic markers in various diseases including cancer, autoimmunity and transplantation. We used microarrays to discover global miRNA expression changes upon PD1 upregulation and identified miRNAs that are both up- and down-regulated. B16F10 cells were injected subcutaneously into C57BL/6 mice and 16 days later CD4+PD1+ and CD4+PD1- were sorted from the lymph nodes and spleen for RNA extraction and hybridization on Affymetrix miRNA array.
2015-08-01 | E-GEOD-65208 | biostudies-arrayexpress
Project description:Expression Profile of Relapsed/Refractory Aggressive B-cell Non Hodgkin Lymphoma Tumors
| PRJNA720938 | ENA
Project description:Hodgkin lymphoma is a haematological malignancy predominantly affecting young adults. Hodgkin lymphoma is a highly curable disease by current treatment standards. Latest treatment guidelines for Hodgkin lymphoma however imply access to diagnostic and treatment modalities that may not be available in settings with restricted healthcare resources. Considerable discrepancies in Hodgkin lymphoma patient survival exist, with poorer outcomes reported in resources-constrained settings. Resources-stratified guidelines for diagnosis, staging and treatment of Hodgkin lymphoma were derived in an effort to optimize patient outcome provided a given setting of available resources. These guidelines were derived based on the framework of the Breast Health Global Initiative stratifying resource levels in basic, core, advanced and maximal categories.
| S-EPMC7084688 | biostudies-literature
Project description:The glycoprotein CD47 regulates antiphagocytic activity via signal regulatory protein alpha (SIRPa). This study investigated CD47 expression on Hodgkin and Reed-Sternberg (HRS) cells in the classical Hodgkin lymphoma (cHL) tumour microenvironment and its correlation with prognosis, programmed-death (PD) immune markers, and SIRPa+ leukocytes. We conducted immunohistochemistry with CD47 and SIRPa antibodies on diagnostic biopsies (tissue microarrays) from cHL patients from two cohorts (n = 178). In cohort I (n = 136) patients with high expression of CD47 on HRS cells (n = 48) had a significantly inferior event-free survival [hazard ratio (HR) = 5.57; 95% confidence interval (CI), 2.78-11.20; p < 0.001] and overall survival (OS) (HR = 8.54; 95% CI, 3.19-22.90; p < 0.001) compared with patients with low expression (n = 88). The survival results remained statistically significant in multivariable Cox regression adjusted for known prognostic factors. In cohort II (n = 42) high HRS cell CD47 expression also carried shorter event-free survival (EFS) (HR = 5.96; 95% CI, 1.20-29.59; p = 0.029) and OS (HR = 5.61; 95% CI, 0.58-54.15; p = 0.136), although it did not retain statistical significance in the multivariable analysis. Further, high CD47 expression did not correlate with SIRPa+ leukocytes or PD-1, PD-L1 and PD-L2 expression. This study provides a deeper understanding of the role of CD47 in cHL during an era of emerging CD47 therapies.
| S-EPMC9310712 | biostudies-literature
Project description:ViPOR in Relapsed/Refractory B-Cell Lymphoma
| PRJNA1090979 | ENA