Trial watch: chemotherapy-induced immunogenic cell death in oncology

OncoImmunology, Год журнала: 2023, Номер 12(1)

Опубликована: Июнь 3, 2023

Immunogenic cell death (ICD) refers to an immunologically distinct process of regulated that activates, rather than suppresses, innate and adaptive immune responses. Such responses culminate into T cell-driven immunity against antigens derived from dying cancer cells. The potency ICD is dependent on the immunogenicity cells as defined by antigenicity these their ability expose immunostimulatory molecules like damage-associated molecular patterns (DAMPs) cytokines type I interferons (IFNs). Moreover, it crucial host’s system can adequately detect adjuvanticity Over years, several well-known chemotherapies have been validated potent inducers, including (but not limited to) anthracyclines, paclitaxels, oxaliplatin. ICD-inducing chemotherapeutic drugs serve important combinatorial partners for anti-cancer immunotherapies highly immuno-resistant tumors. In this Trial Watch, we describe current trends in preclinical clinical integration chemotherapy existing immuno-oncological paradigms.

Язык: Английский

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Emerging Trends in Neuroblastoma Diagnosis, Therapeutics, and Research

Molecular Neurobiology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 13, 2025

Язык: Английский

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Targeting the myeloid microenvironment in neuroblastoma

Journal of Experimental & Clinical Cancer Research, Год журнала: 2023, Номер 42(1)

Опубликована: Дек. 13, 2023

Abstract Myeloid cells (granulocytes and monocytes/macrophages) play an important role in neuroblastoma. By inducing a complex immunosuppressive network, myeloid pose challenge for the adaptive immune system to eliminate tumor cells, especially high-risk This review first summarizes pro- anti-tumorigenic functions of including granulocytes, monocytes, macrophages, myeloid-derived suppressor (MDSC) during development progression Secondly, we discuss how are engaged current treatment regimen explore novel strategies target these These include: (1) engaging as effector (2) ablating or blocking recruitment microenvironment (3) reprogramming cells. Here describe that despite their traits, tumor-associated can still be which is clear anti-GD2 immunotherapy. However, full potential not yet reached, cell engagement enhanced, example by targeting CD47/SIRPα axis. Though depletion infiltration has been proven effective, this strategy also depletes possible immunotherapy from microenvironment. Therefore, suppressive might optimal strategy, reverses preserves effectors immunotherapy, subsequently reactivates tumor-infiltrating T

Язык: Английский

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The neuroblastoma tumor microenvironment: From an in-depth characterization towards novel therapies

EJC Paediatric Oncology, Год журнала: 2024, Номер 3, С. 100161 - 100161

Опубликована: Апрель 7, 2024

Neuroblastoma is a cancer of the sympathetic nervous system that develops in young children, either as low-risk or high-risk disease. The tumor microenvironment (TME) now recognized an important player ecosystem may promote drug resistance and immune escape. Targeting TME combination with therapies directly targeting cells therefore represents interesting strategy to prevent emergence improve patient's outcome. development such strategies however requires in-depth understanding landscape, due its high complexity intra inter-tumoral heterogeneity. Various approaches have been used last years characterize non-immune cell populations present tumors neuroblastoma patients, both quantitatively qualitatively, particular use single-cell transcriptomics. It anticipated near future, genomic information will contribute precise approach therapy neuroblastoma.Deciphering mechanisms interaction between stromal key identify novel therapeutic combinations. Over decade, numerous vitro studies vivo pre-clinical experiments immune-competent immune-deficient models identified circumvent Some these formed basis for early phase I II clinical trials children recurrent refractory neuroblastoma. This review summarizes recently published data on characterization landscape various cellular components, molecules pathways activated result tumor-host interactions.

Язык: Английский

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Monocyte and Macrophage in Neuroblastoma: Blocking Their Pro-Tumoral Functions and Strengthening Their Crosstalk with Natural Killer Cells

Cells, Год журнала: 2023, Номер 12(6), С. 885 - 885

Опубликована: Март 13, 2023

Over the past decade, immunotherapy has represented an enormous step forward in fight against cancer. Immunotherapeutic approaches have increasingly become a fundamental part of combined therapies currently adopted treatment patients with high-risk (HR) neuroblastoma (NB). An increasing number studies focus on understanding immune landscape NB and, since this tumor expresses low or null levels MHC class I, development new strategies aimed at enhancing innate immunity, especially Natural Killer (NK) cells and macrophages. There is growing evidence that, within microenvironment (TME), tumor-associated macrophages (TAMs), which mainly present M2-like phenotype, crucial role mediating evasion, they been correlated to poor clinical outcomes. Importantly, TAM can also impair antibody-dependent cellular cytotoxicity (ADCC) mediated by NK upon administration anti-GD2 monoclonal antibodies (mAbs), current standard for HR-NB patients. This review deals main mechanisms regulating crosstalk among TAMs other components TME, support induce drug resistance. Furthermore, we will address most recent limiting pro-tumoral reprogramming functional state, thus cell functions. We prospectively discuss unexplored aspects human macrophage heterogeneity.

Язык: Английский

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Integrated Microbiome and Metabolome Analysis Reveals Correlations Between Gut Microbiota Components and Metabolic Profiles in Mice With Mitoxantrone-Induced Cardiotoxicity

Drug Design Development and Therapy, Год журнала: 2025, Номер Volume 19, С. 439 - 455

Опубликована: Янв. 1, 2025

Purpose: Mitoxantrone (MTX) is largely restricted in clinical usage due to its significant cardiotoxicity.Multiple studies have shown that an imbalance the gut-heart axis plays important role development of cardiovascular disease (CVD).We aim explore possible correlations between gut microbiota (GM) compositions and cardiometabolic (CM) disorder MTX-triggered cardiotoxicity mice.Methods: MTX cumulative dose 6 mg/kg was administered healthy Kunming male mice trigger cardiotoxicity, with 1 twice weekly for a duration 3 weeks.Plasma CK-MB LDH levels were determined, heart tissue histopathology assessed, followed by utilizing integrated liquid chromatography-mass spectrometry (LC-MS)-based metabolomics study alongside 16S ribosomal RNA (rRNA) sequencing method assess impact on GM CM profiles mice, establishing associations through Pearson correlation coefficient calculation.Results: caused level elevations our mouse model.MTX primarily affected processes protein digestion absorption, mineral membrane transport, production aminoacyl-transfer (tRNA), metabolism nucleotides, lipids, amino acids, as well autophagy.Additionally, increased Romboutsia, Enterococcus, Turicibacter abundances lowered norank_f__Muribaculaceae, Alistipes, Odoribacter, norank_f__Lachnospiraceae, norank_f__Ruminococcaceae, norank_f__Oscillospiraceae, unclassified_f__Ruminococcaceae, NK4A214_group, Colidextribacter, norank_f__norank_o__Clostridia_vadinBB60_group, Rikenella, Anaerotruncus abundances.The analyses showcased variations abundance diverse flora, such Turicibacter, which related MTX-induced cardiac injury.Conclusion: Our supports claim provokes modifying profiles.Our results offer new possibilities controlling cardiotoxicity.

Язык: Английский

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Immunogenic Cell Death Inducers in Cancer Immunotherapy to Turn Cold Tumors into Hot Tumors

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(4), С. 1613 - 1613

Опубликована: Фев. 14, 2025

The combination of chemotherapeutic agents with immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment. However, its success is often limited by insufficient priming in certain tumors, including pediatric malignancies. In this report, we explore clinical trials currently investigating the use immunogenic cell death (ICD)-inducing chemotherapies ICIs for both adult and cancers. Given data available focused on recent preclinical studies evaluating efficacy these combinations neuroblastoma (NB). Finally, to address gap, propose an innovative strategy assess impact ICD-inducing antitumor responses NB. Using tumor spheroids derived from a transgenic NB mouse model, validated our previous vivo findings concerning how anthracyclines, specifically mitoxantrone doxorubicin, significantly enhance MHC class I surface expression, stimulate IFNγ granzyme B production CD8+ T cells NK cells, promote recruitment. Importantly, anthracyclines also upregulated PD-L1 expression spheroids. This screening platform yielded results similar findings, demonstrating that doxorubicin are most potent immunomodulatory These suggest creation libraries ICD inducers be tested could reduce number vivo, line principles 3Rs. Furthermore, highlight potential chemo-immunotherapy regimens counteract immunosuppressive microenvironment NB, paving way improved therapeutic strategies They provide compelling evidence support further investigations outcomes children

Язык: Английский

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An atlas of single-cell eQTLs dissects autoimmune disease genes and identifies novel drug classes for treatment

Cell Genomics, Год журнала: 2025, Номер unknown, С. 100820 - 100820

Опубликована: Март 1, 2025

Most variants identified from genome-wide association studies (GWASs) are non-coding and regulate gene expression. However, many risk loci fail to colocalize with expression quantitative trait (eQTLs), potentially due limited GWAS eQTL analysis power or cellular heterogeneity. Population-scale single-cell RNA-sequencing (scRNA-seq) datasets emerging, enabling mapping of eQTLs in different cell types (sc-eQTLs). Compared data bulk tissues (bk-eQTLs), sc-eQTL smaller. We propose a joint model bk-eQTLs as weighted sum sc-eQTLs (JOBS) constituent improve power. Applying JOBS One1K1K eQTLGen data, we identify 586% more eQTLs, matching the 4× sample sizes OneK1K. Integrating creates an atlas for 14 immune-mediated disorders, colocalizing 29.9% 32.2% than using bk-eQTL alone. Extending JOBS, develop drug-repurposing pipeline novel drugs validated by real-world data.

Язык: Английский

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The NET-DNA-CCDC25 inhibitor di-Pal-MTO suppresses tumor progression and promotes the innate immune response

Cellular and Molecular Immunology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 14, 2025

Язык: Английский

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Repurposing Anthracycline Drugs as Potential Antibiotic Candidates and Potentiators to Tackle Multidrug-Resistant Pathogens

ACS Infectious Diseases, Год журнала: 2024, Номер 10(2), С. 594 - 605

Опубликована: Янв. 6, 2024

The escalating mortality rate resulting from multidrug-resistant (MDR) bacteria has intensified the urgency for innovative antimicrobial agents. Currently, activity of compounds is usually assessed by testing minimum inhibitory concentration (MIC) on a standardized laboratory medium. However, such screening conditions differ in vivo environment, making it easy to overlook some antibacterial agents that are active but less vitro. Herein, using tissue medium RPMI, we uncover anthracyclines, especially mitoxantrone (MX), exhibit improved bacteriostatic and bactericidal effects against various MDR host-like media. Transcriptome results reveal LPS modification-related genes bacterial membrane surfaces metabolic significantly down-regulated RPMI Mechanistic studies demonstrate MX leads more substantial damage, increased ROS production, DNA damage host-mimicking conditions. Furthermore, colistin strong synergistic mcr-positive strains media disrupting iron homeostasis. In an experimental murine infection model, monotreatment demonstrates therapeutic efficacy reducing burdens. Overall, our work suggests mimicking host condition effective strategy identify new highlights potential anthracycline drugs combating pathogens.

Язык: Английский

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