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Immunologic predictors for clinical responses during immune checkpoint blockade in patients with myelodysplastic syndromes

ABSTRACT: We investigated the immune-related gene expression signature in the tumor immune-microenvironment associated with response or resistance during immunotherapy, by performing targeted gene expression profiling and gene set enrichment analysis using a custom NanoString panel composed of 579 immune-related genes

ORGANISM(S): Homo sapiens

PROVIDER: GSE219085 | GEO | 2022/12/29

REPOSITORIES: GEO

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Immunologic Predictors for Clinical Responses during Immune Checkpoint Blockade in Patients with Myelodysplastic Syndromes.

Project description:PurposeThe aim of this study is to determine immune-related biomarkers to predict effective antitumor immunity in myelodysplastic syndrome (MDS) during immunotherapy (IMT, αCTLA-4, and/or αPD-1 antibodies) and/or hypomethylating agent (HMA).Experimental designPeripheral blood samples from 55 patients with MDS were assessed for immune subsets, T-cell receptor (TCR) repertoire, mutations in 295 acute myeloid leukemia (AML)/MDS-related genes, and immune-related gene expression profiling before and after the first treatment.ResultsClinical responders treated with IMT ± HMA but not HMA alone showed a significant expansion of central memory (CM) CD8+ T cells, diverse TCRβ repertoire pretreatment with increased clonality and emergence of novel clones after the initial treatment, and a higher mutation burden pretreatment with subsequent reduction posttreatment. Autophagy, TGFβ, and Th1 differentiation pathways were the most downregulated in nonresponders after treatment, while upregulated in responders. Finally, CTLA-4 but not PD-1 blockade attributed to favorable changes in immune landscape.ConclusionsAnalysis of tumor-immune landscape in MDS during immunotherapy provides clinical response biomarkers.

| S-EPMC10192218 | biostudies-literature

Immunologic predictors for clinical responses during immune checkpoint blockade in patients with myelodysplastic syndromes

Project description:Immunologic predictors for clinical responses during immune checkpoint blockade in patients with myelodysplastic syndromes

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APCIM_Nanostring_HD

Project description:Expression of immune related genes in 12 healthy donors. Expression assessed by analyzing whole blood-derived RNA samples using a Nanostring nCounter Immunology V2 panel (579 genes)

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APCIM_Nanostring_FAP

Project description:Expression of immune related genes in 12 familial adenomatous polyposis patients. Expression assessed by analyzing whole blood-derived RNA samples using a Nanostring nCounter Immunology V2 panel (579 genes)

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Clinical and Immunologic Activity of a Single Dose of Neoadjuvant PD-1 Blockade and Predictors of Clinical Outcomes in Resectable Melanoma

Project description:To understand some of the potential determinants of anti-PD-1 response and resistance in this cohort we used Nanostring analysis to study/compare the expression of custom set of genes

2019-02-11 | GSE123728 | GEO

The Rising Era of Immune Checkpoint Inhibitors in Myelodysplastic Syndromes.

Project description:Myelodysplastic syndromes (MDS) are a heterogeneous group of diseases characterized by ineffective hematopoiesis and a wide spectrum of manifestations ranging from indolent and asymptomatic cytopenias to acute myeloid leukemia (AML). MDS result from genetic and epigenetic derangements in clonal cells and their surrounding microenvironments. Studies have shown associations between MDS and other autoimmune diseases. Several immune mechanisms have been identified in MDS, suggesting that immune dysregulation might be at least partially implicated in its pathogenesis. This has led to rigorous investigations on the role of immunomodulatory drugs as potential treatment options. Epigenetic modification via immune check point inhibition, while well established as a treatment method for advanced solid tumors, is a new approach being considered in hematologic malignancies including high risk MDS. Several trials are looking at the efficacy of these agents in MDS, as frontline therapy and in relapse, both as monotherapy and in combination with other drugs. In this review, we explore the utility of immune checkpoint inhibitors in MDS and current research evaluating their efficacy.

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Immune Checkpoint Inhibition in Acute Myeloid Leukemia and Myelodysplastic Syndromes.

Project description:Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of many solid tumors, with limited progress made in the area of myeloid malignancies. The low mutational burden of acute myeloid leukemia (AML) is one potential reason behind the lack of activity of T-cell harnessing ICIs, particularly CTLA-4 and PD-1 inhibitors. Innate immune checkpoints play a critical role in the immune escape of AML and myelodysplastic syndromes (MDS). The CD47 targeting agent, magrolimab, has shown promising activity when combined with azacitidine in early phase trials conducted in AML and higher-risk MDS, especially among patients harboring a TP53 mutation. Similarly, sabatolimab (an anti-TIM-3 monoclonal antibody) plus hypomethylating agents have shown durable responses in higher-risk MDS and AML in early clinical trials. Randomized trials are currently ongoing to confirm the efficacy of these agents. In this review, we will present the current progress and future directions of immune checkpoint inhibition in AML and MDS.

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Platelet transfusions and predictors of bleeding in patients with myelodysplastic syndromes.

Project description:ObjectivesThis study aimed to describe the burden of thrombocytopenia, supportive care practices, bleeding complications and predictors of bleeding in MDS patients within a large Australian hospital network, to better understand the use and effectiveness of platelet transfusions in MDS.MethodsA retrospective cohort study of patients aged ≥18 years with MDS, chronic myelomonocytic leukaemia or MDS/myeloproliferative overlap neoplasm admitted from 2016 to 2018 was conducted. Data were obtained from hospital medical records.ResultsOne hundred seventy-nine patients (median age 78 years, 61.5% male) were identified. The median platelet count at first admission was 90 × 109 /L. Twenty-eight (15.6%) patients had severe thrombocytopenia (platelet count <20 × 109 /L), of whom nine (32.1%) received prophylactic platelet transfusions, five (17.9%) received tranexamic acid (TXA), seven (25%) received both platelet transfusions and TXA, and seven (25%) received no treatment. Bleeding events requiring hospitalisation occurred in 20 (11.2%) patients. Bleeding was not predicted by presenting platelet count, TXA use, platelet transfusion or anticoagulant/antiplatelet therapies. Three patients died of bleeding, at varying platelet counts (18, 38 and 153 × 109 /L).ConclusionThrombocytopenia is common in MDS. Although guidelines recommend otherwise, prophylactic platelet transfusions were commonly used for severe thrombocytopenia. Despite the majority of patients receiving platelet transfusions and/or TXA, 11% developed major bleeding occurring at a wide range of platelet counts.

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Aristolochic acid-related renal cell carcinoma exhibits a distinct tumor immune microenvironment and may be more responsive to immune checkpoint blockade

Project description:We aimed to investigate the immune profile of AA-related RCC and explore its potential role as a predictive biomarker for ICB. Three distinct clusters were found through functional pathway analysis using the NanoString gene expression panel. AA-positive ccRCC comprised the majority of cluster 1 and 3, and the two patients with good response to ICB were grouped to Cluster 3. Cluster 3 exhibited higher tumor inflammation signature (TIS) and immune cell type scores.

2024-08-21 | GSE275422 | GEO

Myelodysplastic syndromes.

Project description:The myelodysplastic syndromes are a diverse group of clonal stem cell disorders characterized by ineffective hematopoiesis, peripheral cytopenias, and an increased propensity to evolve to acute myeloid leukemia. The molecular pathogenesis of these disorders is poorly understood, but recurring chromosomal abnormalities occur in approximately 50% of cases and are the focus of much investigation. The availability of newer molecular techniques has allowed the identification of additional genetic aberrations, including mutations and epigenetic changes of prognostic and potential therapeutic importance. This review focuses on the key role of cytogenetic analysis in myelodysplastic syndromes in the context of the diagnosis, prognosis, and pathogenesis of these disorders.

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