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PI3Kγ inhibition drives M1 macrophage differentiation and synergizes with PD-L1 blockade to improve survival in poorly immunogenic head and neck squamous cell carcinoma.
[BACKGROUND] Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer globally with high mortality rates, highlighting the urgent need for novel therapeutic strategies. We investigated the efficacy of combining phosphoi…
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Single-cell landscape of peripheral and tumor-infiltrating immune cells in HPV-negative HNSCC.
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. HPV-negative HNSCC, arising in diverse upper airway mucosal niches, is particularly aggressive, with poor 5-y survival and a limited response to immune…
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Lenvatinib potentiates the antitumor efficacy of combined radiotherapy and PD-L1 blockade in lung adenocarcinoma.
[BACKGROUND] The potential of Lenvatinib to synergize with combined radiotherapy and immunotherapy in LUAD remains incompletely characterized. [METHODS] We investigated Lenvatinib's effects on radiation-induced PD-L1 in LUAD cells and VEGF…
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Oncolytic virus OVV-03 enhances CAR-T cell therapy against glioblastoma via immune modulation and specific HER2 upregulation.
Glioblastoma (GBM) remains therapeutically challenging due to treatment resistance and immunosuppression. Oncolytic virotherapy offers a promising strategy. This study engineered OVV-03, a novel HER2-armed oncolytic vesicular stomatitis vir…
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NK cell-mediated tumor cell killing by bispecific innate cell engagers induces ADCC-mediated activation of primary human dendritic cells.
Bispecific antibodies are used for the treatment of hematological malignancies as well as solid tumors. One of their main effector mechanisms is the recruitment of effector cells such as CD8 T cells and CD16A NK cells to tumor cells. Bispec…
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ENPP3 drives ccRCC progression by cGAMP hydrolysis and STING-IFN suppression.
[OBJECTIVE] Clear-cell renal cell carcinoma (ccRCC) is an immune-desert tumor. This study investigates the role of ectonucleotide pyrophosphatase/phosphodiesterase 3 (ENPP3) as a potential therapeutic target and immune-checkpoint enzyme in …
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PD-1 blockade promotes mucosal CD4+ T cell IL-10 production through altering microbiota to reduce intestinal ischemia reperfusion injury.
PD-1 blockade therapy is widely used in clinical practice. Intestinal ischemia reperfusion (IR) injury is a serious clinical complication that leads to remote organ damage through disruption of the gut barrier. However, the effects of PD-1 …
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Prednisolone modulates CD8⁺ and regulatory T-cell activity to dampen response to immune checkpoint inhibitor therapy in melanoma.
Immune checkpoint inhibitors (ICIs) have transformed the treatment of advanced melanoma, yet their efficacy is limited by high-grade immune-related adverse events that often require treatment with systemic corticosteroids. Although corticos…
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Contrasting functions of CD73 and adenosine in CD8+ T-cell exhaustion during antitumor immunity.
T-cell exhaustion is a state of functional decline in T cells, driven by chronic antigen exposure and inhibitory signals within the tumor microenvironment. Exhausted CD8+ T cells (Tex) derive from precursor exhausted T cells (Tpex), a self-…
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Platelets induce VISTA expression and modulate the ovarian tumor microenvironment.
Immune checkpoint regulators, such as the V-domain Ig suppressor of T cell activation (VISTA), play a critical role in shaping the tumor microenvironment (TME) and facilitating immune evasion. In ovarian cancer, VISTA exhibits more abundant…
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Integrating tumor and immune cell transcriptomics to predict immune checkpoint inhibitor primary resistance in metastatic melanoma.
The emergence of immune checkpoint inhibitors (ICIs) has transformed the treatment landscape of metastatic melanoma. However, despite its success, reliable biomarkers for predicting primary resistance are not available in clinical practice.…
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Telomere damage enhances immunogenicity of neuroblastoma and accelerates response to anti-PD-L1 treatment.
Telomerase is active in the majority of high-risk neuroblastomas, a pediatric tumor associated with poor patient outcomes. In other cancer types, resistance to immune checkpoint blockade was overcome by induction of telomere dysfunction usi…
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Gene-level gut microbiome signatures as predictive biomarkers for response to immune checkpoint inhibitors across multiple cancer types.
Targeting programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) with immune checkpoint inhibitors (ICIs) has improved survival across multiple cancer types, but the variability in patient response h…
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DNA prime and peptide boost immunization elicits robust neoantigen-specific CD8 T cell responses and therapeutic protection in mouse tumor models.
Therapeutic immunization against tumor neoantigens has the potential to induce potent and highly selective CD8 T-cell-mediated antitumor immunity. Consequently, immunization strategies that generate robust neoantigen-specific T-cell respons…
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CAR T therapy in adult DLBCL patients in Slovenia: Evaluation of predictive scores for outcomes and adverse events.
CAR T cell therapy is a promising immunotherapy for hematologic malignancies, yet early prediction of outcomes and adverse events remains difficult, especially in small real-world cohorts. We retrospectively analyzed 14 adult patients with …
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Clinical characteristics, treatment options, and prognosis of subcutaneous panniculitis-like T-cell lymphoma from the SEER database.
[INTRODUCTION] Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare type of cutaneous lymphoma lacking standardized treatments. Consequently, patient outcomes vary significantly. [METHODS] This study explored the clinical chara…
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Survival and prognostic features of early-stage diffuse large B-cell lymphoma in older adults.
[BACKGROUND] Early-stage diffuse large B-cell lymphoma (ESDLBCL) in older adults is understudied, and existing prognostic tools such as the stage-adjusted International Prognostic Index (Sa-IPI) may not adequately account for comorbidity an…
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Sialic acid -ligand dynamics modulate Siglec-7 and -9 function and affect Siglec-7/9 co-blockade to potentiate natural killer cell anti-tumor activity.
The glyco-immune checkpoints Siglec-7 and Siglec-9 have received considerable interest as targets for cancer immunotherapy. How Siglec-7/9-sialic acid -interactions on immune cells influence -signaling induced by tumor cells and whether Sig…
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VGLL4 regulates the Wnt/β-catenin signaling pathway and acts as an oncogenic factor in acute myeloid leukemia.
[OBJECTIVE] To investigate the expression, function, and underlying mechanism of VGLL4 in AML. [METHODS] Bioinformatic analysis of TCGA data by GEPIA website was performed. VGLL4 protein expression was analyzed by Western blot. We then per…
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Spatial transcriptomics unveils immune cellular ecosystems associated with patient survival in diffuse large B-cell lymphoma.
Diffuse large B-cell Lymphoma (DLBCL) is the most prevalent subtype of non-Hodgkin's lymphoma for which current therapeutic strategies remain insufficient, in part owing to heterogeneity in tumor biology and the immune microenvironment. The…
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