Modern Pathology, Journal Year: 2024, Volume and Issue: unknown, P. 100624 - 100624
Published: Sept. 1, 2024
Language: Английский
Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15
Published: March 14, 2024
Background Cervical cancer poses a significant global threat to women’s health. However, current therapeutic interventions, such as radiotherapy, chemotherapy, surgical resection, and immune checkpoint inhibitors, face limitations in the advanced stages of disease. Given immunosuppressive microenvironment cervical cancer, it is imperative explore novel perspectives. In this regard, STING agonists have emerged promising candidates. Methods The expression profiles clinicopathological data were obtained from Cancer Genome Atlas (TCGA) Gene Expression Omnibus (GEO) datasets. Prognostic analysis downstream genes (CCL5, CXCL9, CXCL10) infiltration conducted using Kaplan-Meier Plotter, ESTIMATE, deconvo_CIBERSOR . Single-cell RNA-seq (scRNA-seq) was evaluate potential MSA-2 treatment employing SingleR, chi-squared test, Set Enrichment Analysis (GSEA). Cellular interaction utilized CellChat package assess potentiation cellular following administration. Murine tumor models involving U14 TC-1, conducted, IF tissue subsequently status after treatment. Results Prognosis correlated with elevated genes, indicating prolonged survival reduced recurrence. These positively infiltration, influencing stromal scores, estimate scores. Specific cell populations, including CD8 + T cells, M1-type macrophages, NK follicular helper associated genes. scRNA-seq classic immune-excluded model revealed that exerts priming activating functions on vital components within TME, intensifies their intercellular communications. vivo assay ultimately demonstrated MSA-2, either standalone or combination anti-PD-1, effectively suppressed growth subcutaneous tumors. Moreover, strategy significantly augmented efficacy compared anti-PD-1 monotherapy by eliciting robust antitumor response. Conclusion This study highlights pivotal role pathway reshaping cancer. Combining inhibitors presents transformative approach, holding promise for improved prognosis. Further investigations are warranted broader landscape long-term effects
Language: Английский
Citations
9
Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)
Published: March 5, 2025
Language: Английский
Citations
1
Gut, Journal Year: 2024, Volume and Issue: unknown, P. gutjnl - 332837
Published: Sept. 30, 2024
Background The determinants of the response to checkpoint immunotherapy in hepatocellular carcinoma (HCC) remain poorly understood. organisation immune tumour microenvironment (TME) is expected govern outcomes but spatial immunotypes defined. Objective We hypothesised that deconvolution network architectures could identify clinically relevant HCC. Design conducted highly multiplexed imaging mass cytometry on HCC tissues from 101 patients. performed in-depth single-cell analysis a discovery and validation cohort deconvolute heterogeneity architecture develop classification was tested for prediction inhibitor (ICI) therapy. Results Bioinformatic identified 23 major immune, stroma, parenchymal cell types TME. Unsupervised neighbourhood detection based interaction cells three with differing involvement checkpoints dominated by either CD8 T-cells, myeloid or B- CD4 T-cells. used these define reflect higher level intratumour organisation: depleted, compartmentalised enriched. Progression-free survival under ICI therapy differed significantly between improved enriched In patients heterogeneity, presence one area governed long-term survival.
Language: Английский
Citations
8
Cancer Research Communications, Journal Year: 2024, Volume and Issue: 4(4), P. 970 - 985
Published: March 22, 2024
Abstract Immunotherapies for cancers of epithelial origin have limited efficacy, and a growing body evidence links the composition extracellular matrix (ECM) with likelihood favorable response to treatment. The ECM may be considered an immunologic barrier, restricting localization cytotoxic immune cells stromal areas inhibiting their contact tumor cells. Identifying components this barrier could provide targets that whether degraded in situ support antitumor immunity improve immunotherapy response. Using library primary triple-negative breast cancer tissues, we correlated CD8+ T-cell identified proteoglycan, versican (VCAN), as putative member barrier. Our analysis reveals associates location VCAN expression, specific glycovariant [defined through pattern posttranslational attachments glycosaminoglycans (GAG)], cell types produce variant. In functional studies, isomers chondroitin sulfate presented on opposing roles being either supportive or trafficking, removal GAGs ameliorates these effects trafficking. Overall, conclude can inhibit trafficking within microenvironment depending present, is major component defines type immunotherapy. Significance: has been poor toward solid tumors despite infiltrating into tumor. associated impacting infiltration article its structural modification, having key role invasion.
Language: Английский
Citations
7
Science Immunology, Journal Year: 2024, Volume and Issue: 9(94)
Published: April 26, 2024
T cells are often absent from human cancer tissues during both spontaneously induced immunity and therapeutic immunotherapy, even in the presence of a functional cell-recruiting chemokine system, suggesting existence cell exclusion mechanisms that impair infiltration. Using genome-wide vitro screening platform, we identified role for phospholipase A2 group 10 (PLA2G10) protein exclusion. PLA2G10 up-regulation is widespread cancers associated with poor infiltration tumor tissues. overexpression immunogenic mouse tumors excluded infiltration, resulting resistance to anti-PD-1 immunotherapy. can hydrolyze phospholipids into small lipid metabolites, thus inhibiting chemokine-mediated mobility. Ablation PLA2G10's enzymatic activity enhanced sensitized PLA2G10-overexpressing immunotherapies. Our study implicates suggests potential target
Language: Английский
Citations
7
Journal for ImmunoTherapy of Cancer, Journal Year: 2024, Volume and Issue: 12(7), P. e009550 - e009550
Published: July 1, 2024
Background Approximately 50% of head and neck squamous cell carcinomas (HNSCC) recur after treatment with curative intent. Immune checkpoint inhibitors are options for recurrent/metastatic HNSCC; however, less than 20% patients respond. To increase this response rate, it is fundamental to our understanding the spatial tumor immune microenvironment (TIME). Methods In total, 53 HNSCC specimens were included. Using a seven-color multiplex immunohistochemistry panel we identified cells, CD163+macrophages, B CD8+T CD4+T helper cells regulatory T (Tregs) in treatment-naive surgical resection (n=29) biopsies (n=18). further characterize tumor-infiltrating stained (n=12) five-color tumor-resident including CD103, Ki67, CD8 pan-cytokeratin. Secretome analysis was performed on matched suspensions (n=11) measure protein levels. Results Based infiltrates, four different immunotypes: fully infiltrated, stroma-restricted, immune-excluded, immune-desert. We found higher cytokine levels infiltrated tumors compared other immunotypes. While highest infiltrates observed invasive margin all CD163+macrophages Tregs had tendency infiltrate center. Within center, especially stayed at stroma, whereas followed by more often localized within fields. Also, away from formed aggregates while tended be closely located each other. Across various anatomical sites neck, oral cavity exhibited densities Tregs. Moreover, distance shortest carcinoma (OCSCC), suggesting interaction between lymphocytes cells. fraction 10 µm lowest OCSCC, indicating fewer myeloid/T-cell suppressive interactions OCSCC. Conclusions comprehensively described TIME using unique data set specimens. discovered that composition, as well relative localization TIME, differed distinct neck.
Language: Английский
Citations
6
Neuro-Oncology, Journal Year: 2023, Volume and Issue: 26(2), P. 211 - 225
Published: Nov. 23, 2023
Abstract Glioblastoma (GBM)’s median overall survival is almost 21 months. Six phase 3 immunotherapy clinical trials have recently been published, yet 5/6 did not meet approval by regulatory bodies. For the sixth, uncertain. Trial failures result from multiple factors, ranging intrinsic tumor biology to trial design. Understanding and basic science of these 6 compelled other immunotherapies reaching point advanced testing. We need understand more in human GBMs early trials: “window opportunity” design may be best complex changes brought about immunotherapeutic perturbations GBM microenvironment. The convergence increased safety image-guided biopsies with “multi-omics” small cell numbers now permits longitudinal sampling biofluids dissect temporal microenvironment as a function immunotherapy.
Language: Английский
Citations
16
Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14
Published: July 3, 2023
This review focuses on the immunosuppressive effects of tumor angiogenesis and coagulation microenvironment (TME). We summarize previous research efforts leveraging these observations targeting processes to enhance immunotherapy outcomes. Clinical trials have documented improved outcomes when combining anti-angiogenic agents immunotherapy. However, their overall survival benefit over conventional therapy remains limited certain tumors exhibit poor response therapy. Additionally, whilst preclinical studies shown several components coagulome curb effective anti-tumor immune responses, clinical reporting combinations anticoagulants with immunotherapies demonstrated variable treatment By reviewing current state literature this topic, we address key questions future directions in field, answers which are crucial for developing strategies reprogram TME order further field cancer
Language: Английский
Citations
12
Frontiers in Oncology, Journal Year: 2023, Volume and Issue: 13
Published: May 22, 2023
Immunotherapy has changed the course of cancer treatment. The initial steps were made through tumor-specific antibodies that guided setup an antitumor immune response. A new and successful generation are designed to target checkpoint molecules aimed reinvigorate cellular counterpart is adoptive cell therapy, where specific cells expanded or engineered cells. In all cases, key for achieving positive clinical resolutions rests upon access tumor. this review, we focus on how tumor microenvironment architecture, including stromal cells, immunosuppressive extracellular matrix, protects from attack leading immunotherapy resistance, available strategies tackle evasion.
Language: Английский
Citations
11
Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)
Published: July 16, 2024
Abstract The epigenetic regulation of N6-methyladenosine (m 6 A) has attracted considerable interest in tumor research, but the potential roles m A regulator-related genes, remain largely unknown within context gastric cancer (GC) and microenvironment (TME). Here, a comprehensive strategy data mining computational biology utilizing multiple datasets based on 28 regulators (including novel anti-readers) was employed to identify genes patterns elucidate their underlying mechanisms GC. Subsequently, scoring system constructed evaluate individual prognosis immunotherapy response. Three distinct were identified through unsupervised clustering 56 (all significantly associated with GC prognosis). TME characterization revealed that these highly corresponded immune-inflamed, immune-excluded, immune-desert phenotypes, characteristics consistent different clinical outcomes biological processes. Additionally, an A-related developed quantify modification pattern samples. Low scores indicated high survival rates levels immune activation, whereas stromal activation malignancy. Furthermore, correlated mutation loads various traits, including molecular or histological subtypes stage grade, score had predictive values across all digestive tumors even types. Notably, low linked improved responses anti-PD-1/L1 anti-CTLA4 three independent cohorts. This study expanded important role shaping diversity clinical/biological traits could help develop more effective strategies personalized treatment guidance.
Language: Английский
Citations
4