Increased Co-Expression of PD-L1 and CTLA-4 Predicts Poor Overall Survival in Patients with Acute Myeloid Leukemia Following Allogeneic Hematopoietic Stem Cell Transplantation.

Purpose: Our previous study has demonstrated that high expression of immune checkpoints (ICs) was significantly associated with adverse clinical outcomes in patients with acute myeloid leukemia (AML). This study aims to investigate the significance of the alteration of IC co-expression for evaluating the prognosis of AML patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Patients And Methods: Quantitative real-time PCR (qRT-PCR) data of bone marrow (BM) samples from 62 de novo AML patients, including 37 patients who received allo-HSCT and 25 patients who received chemotherapy only, were used for prognostic analysis.

Sex-Biased CD3ζ 3'-UTR SNP Increased Incidence Risk in Aplastic Anemia.

Purpose: Aplastic anemia (AA) is a bone marrow failure syndrome with an unclear pathogenesis. Abnormal T cell immunity is one of the mechanisms involved in AA, and CD3ζ is an important signaling molecule for T cell activation. Single-nucleotide polymorphisms (SNPs) in CD3ζ 3'-untranslated region (3'-UTR) were associated with some immune-related disease occurrence and affect CD3ζ protein level.

Single-Cell Multiomics Reveals TCR Clonotype-Specific Phenotype and Stemness Heterogeneity of T-ALL Cells.

T-cell acute lymphoblastic leukaemia (T-ALL) is a heterogeneous malignant disease with high relapse and mortality rates. To characterise the multiomics features of T-ALL, we conducted integrative analyses using single-cell RNA, TCR and chromatin accessibility sequencing on pre- and post-treatment peripheral blood and bone marrow samples of the same patients. We found that there is transcriptional rewiring of gene regulatory networks in T-ALL cells.

exon 20 insertion mutation and exon 14 skipping mutation in non-small cell lung cancer: a scoping review in the Chinese population.

Background: Epidermal growth factor receptor () and mesenchymal-epithelial transition () gene mutations are well established in the pathogenesis of non-small cell lung cancer (NSCLC). However, there is limited understanding about the impact of rare variants, such as exon 20 insertion mutation (ex20ins) and exon 14 skipping mutation (ex14) in the Chinese population even though targeted therapies have been approved in China. We conducted a scoping review to assess the current available evidence of these two mutations in NSCLC in the Chinese population.

Inhibition of TOX exerts anti-tumor effects in acute myeloid leukemia by upregulating IRF7 expression.

Thymocyte selection-associated high mobility group box protein (TOX) is regarded as a crucial transcription factor involved in T cell exhaustion in acute myeloid leukemia (AML). Previous studies have identified aberrant TOX expression as a major oncogenic driver in hematologic malignancies, indicating that TOX may potentially be both an immune biomarker and an immunotherapy target. However, due to heterogeneity in the distribution patterns of TOX and its correlation with clinical prognosis, the mechanism underlying TOX-mediated tumor immune responses remains unclear.

Aptamer sgc8-Modified PAMAM Nanoparticles for Targeted siRNA Delivery to Inhibit BCL11B in T-Cell Acute Lymphoblastic Leukemia.

Introduction: T-cell acute lymphoblastic leukemia (T-ALL) is a malignant hematological disease with limited targeted therapy options. Overexpression of B-cell lymphoma/leukemia 11B is frequently observed in T-ALL and contributes to leukemogenesis. Knockdown of BCL11B inhibits T-ALL cell proliferation and induces apoptosis, making it a potential therapeutic target.

BRD4 inhibitor reduces exhaustion and blocks terminal differentiation in CAR-T cells by modulating BATF and EGR1.

Background: Exhaustion is a key factor that influences the efficacy of chimeric antigen receptor T (CAR-T) cells. Our previous study demonstrated that a bromodomain protein 4 (BRD4) inhibitor can revise the phenotype and function of exhausted T cells from leukemia patients. This study aims to elucidate the mechanism by which a BRD4 inhibitor reduces CAR-T cell exhaustion using single-cell RNA sequencing (scRNA-Seq).

Triclocarban disrupts the activation and differentiation of human CD8 T cells by suppressing the vitamin D receptor signaling.

Triclocarban (TCC) is a widely applied environmental endocrine-disrupting chemical (EDC). Similar to most of EDCs, TCC potentially damages the immunity of various species. However, whether and how TCC impacts the adaptive immunity in mammals has yet to be determined.

Dual role of in T-cell malignancies.

The zinc finger transcription factor B-cell CLL/lymphoma 11B gene (, ) plays a crucial role in T-cell development, but its role in T-cell malignancies has not yet been definitively clarified. In the literature, 2 contradictory hypotheses on the function of exist. One suggests that functions as tumor suppressor gene, and the other suggests that functions as oncogene.

Spatial Proteomic Profiling of Colorectal Cancer Revealed Its Tumor Microenvironment Heterogeneity.

Colorectal cancer is a predominant malignancy with a second mortality worldwide. Despite its prevalence, therapeutic options remain constrained and surgical operation is still the most useful therapy. In this regard, a comprehensive spatially resolved quantitative proteome atlas was constructed to explore the functional proteomic landscape of colorectal cancer.

BET Inhibitor JQ1 Selectively Reduce Tregs by Upregulating STAT3 and Suppressing PD-1 Expression in Patients with Multiple Myeloma.

Multiple myeloma (MM) stands as a prevalent hematological malignancy, primarily incurable, originating from plasma cell clones. MM's progression encompasses genetic abnormalities and disruptions in the bone marrow microenvironment, leading to tumor proliferation, immune dysfunction, and compromised treatment outcomes. Emerging evidence highlights the critical role of regulatory T cells (Tregs) in MM progression, suggesting that targeting Tregs could enhance immune functionality and treatment efficacy.

Long-Term Follow-Up of Patients Undergoing Thalidomide Therapy for Transfusion-Dependent β-Thalassaemia: A Single-Center Experience.

Objective: We evaluated the long-term safety and efficacy of thalidomide in the treatment of transfusion-dependent β-thalassemia (TDT).

Methods: Fifty patients with TDT were treated with thalidomide and followed-up for 5 years. Thalidomide at a 50 mg dose was administered once a day after dinner.

Higher TIGIT+ γδ T cells may predict poor prognosis in younger adult patients with non-acute promyelocytic AML.

Introduction: γδ T cells recognize and exert cytotoxicity against tumor cells. They are also considered potential immune cells for immunotherapy. Our previous study revealed that the altered expression of immune checkpoint T-cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT) on γδ T cells may result in immunosuppression and is possibly associated with a poor overall survival in acute myeloid leukemia (AML).

Promoter rs5029924 Concomitant with rs2230926 and rs5029937 May Be a Prognostic Predictor for Joint Deformity or Refractory Rheumatoid Arthritis.

Background: There have been several studies regarding the susceptibility of gene SNPs (rs2230926 and rs5029937) in rheumatoid arthritis (RA). However, little is known about the association between polymorphisms in the promoter and RA. The aim of this study was to investigate the characteristics of promoter polymorphisms and the association between these polymorphisms and clinical significance in Chinese RA patients.

Utilizing exosomes as sparking clinical biomarkers and therapeutic response in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a malignant clonal tumor originating from immature myeloid hematopoietic cells in the bone marrow with rapid progression and poor prognosis. Therefore, an in-depth exploration of the pathogenesis of AML can provide new ideas for the treatment of AML. In recent years, it has been found that exosomes play an important role in the pathogenesis of AML.

Inhibition of NRF2 enhances the acute myeloid leukemia cell death induced by venetoclax via the ferroptosis pathway.

Venetoclax, an inhibitor that selectively targets B cell lymphoma-2 (BCL-2) that has been approved for treating adult acute myeloid leukemia (AML) in combination with hypomethylating agents. However, its short duration of response and emergence of resistance are significant issues. In this study, we found that the sensitivity of AML cells to venetoclax was considerably enhanced by ML385, an inhibitor of the ferroptosis factor nuclear transcription factor erythroid 2-related factor 2 (NRF2).

Immune checkpoint expression patterns on T cell subsets in light-chain amyloidosis: VISTA, PD-1, and TIGIT as potential therapeutic targets.

Amyloid light chain (AL) amyloidosis is a rare plasma cell dyscrasia with dismal prognosis. This study aims to investigate the T-cell immune checkpoint expression patterns in systemic AL amyloidosis and its relationship with clinicobiological traits. We examined the frequencies of V-domain immunoglobulin suppressor of T cell activation (VISTA), programmed cell death 1 (PD-1), T cell immunoglobulin and mucin-domain-containing-3 (Tim-3), T cell immunoreceptor with Ig and ITIM domains (TIGIT) T cells in peripheral blood (PB) and bone marrow (BM) from 19 patients with newly diagnosed AL amyloidosis.

CD69 is a Promising Immunotherapy and Prognosis Prediction Target in Cancer.

Immunotherapy utilizing T cells that attack tumors is a promising strategy for treatment, but immune suppressive T cell subsets, such as regulatory T cell (Treg), and immune checkpoint molecules, including programmed death-1 (PD-1), can suppress the intensity of a T cell immune reaction and thereby impair tumor clearance. Cluster of differentiation 69 (CD69), known as an early leukocyte activation marker, can be used as a measure or early marker of T cell activation. In recent years, the functions of CD69 in the regulation of Treg/Th17 (T helper cell 17) differentiation and in the tissue retention of T cells have attracted considerable interest.

PD-L1 expression guidance on sintilimab versus pembrolizumab with or without platinum-doublet chemotherapy in untreated patients with advanced non-small cell lung cancer (CTONG1901): A phase 2, randomized, controlled trial.

No direct comparison has been performed between different programmed cell death-1 (PD-1) inhibitors for first-line treatment in patients with advanced non-small cell lung cancer (NSCLC). The feasibility of using PD-L1-expression-guided immunotherapy remains unknown. In this open-label, phase 2 study (NCT04252365), patients with advanced NSCLC without EGFR or ALK alterations were randomized (1:1) to receive sintilimab or pembrolizumab monotherapy (PD-L1 expression ≥ 50%), or sintilimab or pembrolizumab plus platinum-based chemotherapy (PD-L1 expression < 50%).