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BET inhibition reforms the immune microenvironment and alleviates T-cell dysfunction in chronic lymphocytic leukemia

ABSTRACT: BET inhibition reforms the immune microenvironment and alleviates T-cell dysfunction in chronic lymphocytic leukemia

PROVIDER: PRJNA1090059 | ENA |

REPOSITORIES: ENA

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BET inhibition reforms the immune microenvironment and alleviates T-cell dysfunction in chronic lymphocytic leukemia

Project description:Redundant tumor microenvironment (TME) immunosuppressive mechanisms and epigenetic maintenance of terminal T-cell exhaustion greatly hinder functional anti-tumor T-cell responses in chronic lymphocytic leukemia (CLL). Bromodomain and extra-terminal (BET) proteins regulate key pathways contributing to CLL pathogenesis and TME interactions, including T-cell function and differentiation. Herein, we report that blocking BET protein function alleviates immunosuppressive networks in the CLL TME and repairs inherent T-cell defects. The pan-BET inhibitor OPN-51107 reduced exhaustion-associated cell signatures, fostering improved T-cell proliferation and effector function in patient samples and murine models of CLL. These findings establish the immunomodulatory action of BET-i on CLL T-cells and support the use of BET inhibitors in treatment strategies for CLL.

2024-05-21 | GSE262027 | GEO

BET inhibition reforms the immune microenvironment and alleviates T-cell dysfunction in chronic lymphocytic leukemia

Project description:BET inhibition reforms the immune microenvironment and alleviates T-cell dysfunction in chronic lymphocytic leukemia

| PRJNA1123777 | ENA

BET inhibition reforms the immune microenvironment and alleviates T-cell dysfunction in chronic lymphocytic leukemia

Project description:BET inhibition reforms the immune microenvironment and alleviates T-cell dysfunction in chronic lymphocytic leukemia

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The Follicular Lymphoma and Chronic Lymphocytic Leukemia Proliferative Microenvironment at Single-Cell Resolution

Project description:Human B cell lymphomas such as Follicular Lymphoma (FL) and Chronic Lymphocytic Leukemia/Small lymphocytic lymphoma (CLL) grow in lymph nodes in areas defined as malignant follicles, and proliferation centers, respectively. We used single-cell RNA-sequencing to study the tumor microenvironment of human lymph nodes involved by FL and CLL.

2024-11-19 | GSE261917 | GEO

Romidepsin in Treating Patients With Lymphoma, Chronic Lymphocytic Leukemia, or Solid Tumors With Liver Dysfunction

Project description:This phase I trial studies the side effects and best dose of romidepsin in treating patients with lymphoma, chronic lymphocytic leukemia, or solid tumors with liver dysfunction. Romidepsin may stop the growth of cancer cells by entering the cancer cells and by blocking the activity of proteins that are important for the cancer’s growth and survival.

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Regulation of GLI underlies a role for BET bromodomains in pancreatic cancer growth and the tumor microenvironment

Project description:Pancreatic ductal adenocarcinoma (PDAC) is extraordinarily chemoresistant and the abundant stromal content of these tumors contributes to the ineffective treatment of this disease. While the genetic alterations of PDAC have been well characterized, the epigenetic pathways regulating PDAC remain, for the most part, elusive. Employing an in vivo shRNA screen targeting epigenetic regulators, we identified members of the BET family of chromatin adaptors as key regulators of PDAC cell growth and maintenance of the tumor stroma. BET family members contribute to PDAC cell growth by modulating the activity of two key transcriptional programs, MYC and GLI. Within the cancer cells, BET inhibition also results in down-regulation of a key mediator of the tumor microenvironment, SHH, corresponding to a decrease in the stromal content of tumors. Taken together, these results suggest that therapeutic inhibition of BET proteins offers a novel mechanism to target both the neoplastic and stromal components of PDAC. Total RNA was isolated from 4 untreated PDAC cell lines or those exposedto the BET bromodomain inhibibitor CPI203 (1.6 uM) or control DMSO for 5 and 10 hours

2016-09-08 | E-GEOD-55209 | biostudies-arrayexpress

Lionheart LincRNA Alleviates Cardiac Systolic Dysfunction under Pressure Overload

Project description:Lionheart LincRNA Alleviates Cardiac Systolic Dysfunction under Pressure Overload

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Unveiling key players in the Chronic Lymphocytic Leukemia (CLL)-microenvironment interplay

Project description:Unveiling key players in the Chronic Lymphocytic Leukemia (CLL)-microenvironment interplay

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Telomere dysfunction and fusion during the progression of chronic lymphocytic leukaemia: evidence for a telomere crisis

Project description:We performed single-molecule telomere length and telomere fusion analysis in patients at different stages of chronic lymphocytic leukaemia (CLL). Our work identified the shortest telomeres ever recorded in primary human tissue reinforcing the concept that there is significant cell division in CLL. Furthermore, we provide direct evidence that critical telomere shortening, dysfunction and fusion contribute to disease progression. The frequency of short telomeres and fusion events increased with advanced disease, but importantly these were also found in a subset of early-stage patient samples indicating that these events can precede disease progression. Sequence analysis of fusion events isolated from individuals with the shortest telomeres revealed limited numbers of repeats at the breakpoint, sub-telomeric deletion and microhomology. Array-CGH analysis of individuals displaying evidence of telomere dysfunction revealed large-scale genomic rearrangements that were concentrated in the telomeric regions; this was not observed in samples with longer telomeres. Array CGH was undertaken on six individuals (five CLL stage C and one stage A) that displayed evidence of telomere dysfunction, and four (three CLL stage A and one stage B) that displayed longer and apparently stable telomeres.

2010-05-28 | E-GEOD-22016 | biostudies-arrayexpress

Regulation of GLI underlies a role for BET bromodomains in pancreatic cancer growth and the tumor microenvironment

2016-09-08 | GSE55209 | GEO