Inducing Cuproptosis with Copper Ion‐Loaded Aloe Emodin Self‐Assembled Nanoparticles for Enhanced Tumor Photodynamic Immunotherapy

Advanced Healthcare Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

Immunotherapy has fundamentally transformed the clinical treatment landscape for non-small cell lung cancer (NSCLC). While its effectiveness is ultimately limited by patient heterogeneity and immunosuppressive tumor microenvironment. Photodynamic therapy (PDT), as an emerging antitumor immunotherapy, shown unique therapeutic advantages. However, previous studies often overlooked potential toxicity of photosensitizers (PS), making discovery safe effective PS a pressing need. In this study, Aloe Emodin (AE), medicinal plant natural compound, was loaded with copper ions (Cu), self-assembled into nanoparticles (NPs) under modification PEG2k-DSPE-FA. NPs can target, accumulate, reside within sites, responsively releasing AE, thus dual-functioning inducing death via cuproptosis enhancing PDT effects. The LLC tumor-bearing mouse model demonstrated that induce maturation dendritic cells (DCs) in vivo, promote lymphocyte infiltration, transform "cold tumors" "hot significantly enhance efficacy immune checkpoint blockade (ICB). This study provides experimental evidence AE clinically promising agent offers novel perspective synergistic NSCLC.

Language: Английский

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Immunomodulation on tumor immune microenvironment in acquired targeted therapy resistance and implication for immunotherapy resistance

Translational Oncology, Journal Year: 2025, Volume and Issue: 54, P. 102353 - 102353

Published: March 8, 2025

Language: Английский

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New insights into cancer immune checkpoints landscape from single-cell RNA sequencing

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2025, Volume and Issue: 1880(3), P. 189298 - 189298

Published: March 13, 2025

Language: Английский

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Targeting tumor-intrinsic S100 calcium-binding protein A1 augments antitumor immunity and potentiates immunotherapy efficacy

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: March 17, 2025

Abstract Immune checkpoint blockade (ICB) has revolutionized cancer treatment, but the therapeutic response is highly heterogeneous, which highlights necessity for developing predictive biomarkers and overcoming ICB resistance. Cancer cell-intrinsic features, especially those that can be dynamically monitored via liquid biopsy, represent a broader scope biomarker development. In addition, potential mode of resistance tumor-intrinsic mechanisms leading to an immunosuppressive tumor microenvironment (TME). However, underlying interactive network remains elusive, generalizable targeting strategies are still lacking. Here, we uncovered plasma S100 calcium-binding protein A1 (S100A1) determining efficacy biopsy patients with lung cancer. Multiomics functional studies have suggested S100A1 expression correlated immunologically “cold” TME in multiple syngeneic murine tumors tissue samples from Mechanistic investigations demonstrated interfering S100A1/ubiquitin-specific protease 7/p65/granulocyte-macrophage colony-stimulating factor (GM-CSF) modulatory axis could potentiate inflamed by promoting M1-like macrophage polarization T cell function. GM-CSF priming was sufficient enhance high preclinical models. These findings define as blood-based novel synergistic target immunotherapy.

Language: Английский

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Resistance in Lung Cancer Immunotherapy and How to Overcome It: Insights from the Genetics Perspective and Combination Therapies Approach

Cells, Journal Year: 2025, Volume and Issue: 14(8), P. 587 - 587

Published: April 12, 2025

Lung cancer with the highest number of new cases diagnosed in Europe and Poland, remains an example malignancy a very poor prognosis despite recent progress medicine. Different treatment strategies are now available for therapy based on its type, molecular subtype other factors including overall health, stage disease profile. Immunotherapy is emerging as potential addition to surgery, chemotherapy, radiotherapy or targeted therapies, but also considered mainstay mode. This combination area active investigation order enhance efficacy overcome resistance. Due complexity dynamic cancer’s ecosystem, novel therapeutic targets need continued research into cellular mechanisms within tumour microenvironment. From genetic point view, several signatures ranging from few mutated genes hundreds them have been identified associated resistance metastatic potential. ML techniques AI can predictive model prognosis. Here, we present overview already existing approaches, current findings key aspects immunotherapy, such immune checkpoint inhibitors (ICIs), biomarkers like PD-L1 expression, mutation burden, immunoscore, neoantigens, well their roles markers response

Language: Английский

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Integrating bulk, single-cell, and spatial transcriptomics to identify and functionally validate novel targets to enhance immunotherapy in NSCLC

npj Precision Oncology, Journal Year: 2025, Volume and Issue: 9(1)

Published: April 16, 2025

Programmed cell deaths (PCDs) are crucial for tumor progression. By analyzing 18 PCDs, we generated a robust multigene signature, Combined Cell Death Index (CCDI), comprising necroptosis and autophagy genes non-small lung cancer (NSCLC). The CCDI accurately stratified patients by survival prognosis predicted immunotherapy responses. We validated prioritized using five single-cell RNA sequencing two spatial transcriptomics datasets. positively correlates with malignancy, invasiveness, resistance. Four (PTGES3, MYO6, CCT6A, CTSH) may affect evolution. In vitro, CTSH overexpression or PTGES3 knockdown inhibited NSCLC proliferation migration while inducing necrosome formation. Moreover, observed diminished CTSH, heightened PTGES3, low activity in 12 pairs of tumors normal tissues. induced improved anti-PD1 therapy efficiency syngeneic mouse models. These findings indicate as potential therapeutic targets treatments.

Language: Английский

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Advancing Cancer Treatment: A Review of Immune Checkpoint Inhibitors and Combination Strategies

Cancers, Journal Year: 2025, Volume and Issue: 17(9), P. 1408 - 1408

Published: April 23, 2025

A groundbreaking milestone in oncology has been the recognition and targeted elimination of malignant cells through cancer immunotherapy, which harnesses body’s immune system to attack [...]

Language: Английский

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USP14-IMP2-CXCL2 axis in tumor-associated macrophages facilitates resistance to anti-PD-1 therapy in gastric cancer by recruiting myeloid-derived suppressor cells

Oncogene, Journal Year: 2025, Volume and Issue: unknown

Published: April 23, 2025

Language: Английский

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Exosome-based immunotherapy in hepatocellular carcinoma

Clinical and Experimental Medicine, Journal Year: 2025, Volume and Issue: 25(1)

Published: April 24, 2025

Language: Английский

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Immune Checkpoint Inhibitors and Immunosuppressive Tumor Microenvironment: Current Challenges and Strategies to Overcome Resistance

Immunopharmacology and Immunotoxicology, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 45

Published: May 16, 2025

Immune checkpoint inhibitors (ICIs) are shown to improve cancer treatment effectiveness by boosting the immune system of patient. Nevertheless, unique and highly suppressive TME poses a significant challenge, causing heterogeneity response or resistance in considerable number patients. This review focuses on evasive attributes TME. evasion mechanism include immunosuppressive cells, cytokine chemokine signaling, metabolic alterations overexpression molecules such as PD-1, CTLA-4, LAG-3, TIM-3, TIGIT, BTLA their interactions within In addition, this overcoming targeting normalizing tumor blood vessels, blocking two three checkpoints simultaneously, combining vaccines, oncolytic viruses with ICIs other therapies. also necessity finding predictive markers for stratification patients check treatment. It remains be made certain new research intelligent innovations how these discoveries its interplay facilitate ICI change face

Language: Английский

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