Advances in genetics, Journal Year: 2024, Volume and Issue: unknown, P. 367 - 409
Published: Jan. 1, 2024
Language: Английский
Nature Cell Biology, Journal Year: 2024, Volume and Issue: 26(4), P. 628 - 644
Published: March 21, 2024
Language: Английский
Citations
21
Journal of Microbiology and Biotechnology, Journal Year: 2023, Volume and Issue: 33(7), P. 849 - 856
Published: March 30, 2023
Language: Английский
Citations
38
Cell Discovery, Journal Year: 2023, Volume and Issue: 9(1)
Published: Nov. 15, 2023
Abstract CD8 + T cell activation via immune checkpoint blockade (ICB) is successful in microsatellite instable (MSI) colorectal cancer (CRC) patients. By comparison, the success of immunotherapy against stable (MSS) CRC limited. Little known about most critical features cells that together determine diverse landscapes and contrasting ICB responses. Hence, we pursued a deep single mapping on transcriptomic receptor (TCR) repertoire levels patient cohort, with additional surface proteome validation. This revealed dynamics are underscored by complex interactions between interferon-γ signaling, tumor reactivity, TCR repertoire, (predicted) antigen-specificities, environmental cues like gut microbiome or colon tissue-specific ‘self-like’ features. MSI showed tumor-specific reminiscent canonical ‘T hot’ tumors, whereas MSS exhibited unspecific bystander-like was accompanied inflammation ‘pseudo-T tumors. Consequently, overlapping phenotypic differed dramatically their antigen-specificities. Given high discriminating potential for features/specificities, used tumor-reactive signaling modules to build bulk transcriptome classification “Immune Subtype Classification” (ISC) successfully distinguished various tumoral prognostic value predicted responses Thus, deliver unique map drives novel landscape classification, relevance decision-making.
Language: Английский
Citations
38
Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 14
Published: Jan. 6, 2025
The current understanding of colorectal carcinogenesis is based on the adenoma-carcinoma sequence, where genetics, intestinal microbiota changes and local immunity shifts seem to play key roles. Despite emerging evidence dysbiotic state immune-cell infiltration in patients with adenocarcinoma, early advanced adenoma as precursors cancer, carcinoma situ following progression, are rather less studied. newly colon-site adapted AI-based analysis immune infiltrates able predict long-term outcomes colon carcinoma. Though it could also facilitate pathologic evaluation precancerous lesion's potential progress. Therefore, purpose this prospective cohort study (MIMICA-1) is, firstly, identify patterns around normal bowel tissue, adenoma, situ, secondly, analyze - microbiome interplay along steps conventional tumorigenesis. This aims prospectively recruit 40 (10 per group) confirmed dysplasia undergoing endoscopic polypectomy, mucosal resection for small (≤1cm), large (>1cm) or biopsy subsequent invasive 10 healthy screening colonoscopy. Stool samples will be collected prior preparation fecal (luminal) composition. Biopsy specimens taken from terminal ileum, right colon, left a pathological lesion (if present) assess mucosa-associated composition response. DNA extracted all sequenced using Illumina MiSeq platform. Unifrac Bray-Curtis methods used microbial diversity. system response examined digital image primarily immunohistochemistry procedures CD3, CD8, CD20 CD68 cell markers performed. Thereafter, count, density distribution immunocompetent cells epithelial stromal tissue compartments evaluated interaction between sequence examined. In addition, explored gut microbiota's composition, comparing fecal- tissue-derived bacterial sequence. We hypothesize that within human led detectable alterations correlate progression mucosa It expectable find more severe at site, though analyzing cancer we expect detect broader luminal near-lesion site possibly throughout entire colon. believe specific compositional differences detected premalignant lesions critically important its primary role initiation acceleration carcinogenesis. Thus, these potentially supplement immunohistochemical tests non-invasive detection adenoma. Moreover, become additional diagnostic prognostic tool development cancer. registered Australian New Zealand Clinical Trials Registry (ACTRN12624000976583) https://www.anzctr.org.au/.
Language: Английский
Citations
1
Cell Biochemistry and Biophysics, Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 13, 2025
Language: Английский
Citations
1
Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14
Published: Sept. 14, 2023
The intestinal mucosa is constantly exposed to commensal microbes, opportunistic pathogens, toxins, luminal components and other environmental stimuli. consists of multiple differentiated cellular extracellular that form a critical barrier, but also equipped for efficient absorption nutrients. Combination genetic susceptibility factors are known as involved in the pathogenesis diseases. innate immune system plays role recognition elimination potential threats by detecting pathogen-associated molecular patterns (PAMPs) damage-associated (DAMPs). This host defense facilitated pattern receptors (PRRs), which cyclic GMP-AMP synthase-stimulator interferon genes (cGAS-STING) pathway has gained attention due its sensing foreign double-stranded DNA (dsDNA) well dinucleotides (CDNs) produced bacteria. Upon binding with dsDNA, cGAS converts ATP GTP (cGAMP), binds STING activates TANK kinase 1 (TBK1) regulatory factor 3 (IRF3), inducing type I (IFN) nuclear kappa B (NF-κB)-mediated pro-inflammatory cytokines, have diverse effects on adaptive cells epithelial (IECs). However, opposite perspectives exist regarding cGAS-STING different Activation signaling associated worse clinical outcomes inflammation-associated diseases, while it protection against tumorigenesis certain infections. Therefore, understanding context-dependent mechanisms physiopathology crucial developing therapeutic strategies targeting pathway. review aims provide insight into recent findings protective detrimental roles
Language: Английский
Citations
17
Cell Biochemistry and Function, Journal Year: 2024, Volume and Issue: 42(4)
Published: May 14, 2024
Colorectal cancer (CRC) is a common digestive tract tumor, with incidences continuing to rise. Although modern medicine has extended the survival time of CRC patients, its adverse effects and financial burden cannot be ignored. multi-step process can caused by disturbance gut microbiome chronic inflammation's stimulation. Additionally, presence precancerous lesions also risk factor for CRC. Consequently, scientists are increasingly interested in identifying multi-target, safe, economical herbal natural products. This paper summarizes berberine's (BBR) regulatory mechanisms occurrence development The findings indicate that BBR regulates homeostasis controls mucosal inflammation prevent In stage, inhibits cell proliferation, invasion, metastasis, blocks cycle, induces apoptosis, metabolism, angiogenesis, enhances chemosensitivity. plays role overall management Therefore, using as an adjunct prevention treatment could become future trend oncology.
Language: Английский
Citations
8
The Oncologist, Journal Year: 2024, Volume and Issue: 29(10), P. 824 - 832
Published: June 26, 2024
Colorectal cancer (CRC) is a major cause of cancer-related deaths globally. While treatment advancements have improved survival rates, primarily through targeted therapies based on KRAS, NRAS, and BRAF mutations, personalized strategies for CRC remain limited. Immunotherapy, mainly immune checkpoint blockade, has shown efficacy in various cancers but effective only small subset patients with deficient mismatch repair (dMMR) proteins or high microsatellite instability (MSI). Recent research challenged the notion that immunologically inert, revealing subsets immunogenicity diverse lymphocytic infiltration. Identifying precise biomarkers beyond dMMR MSI crucial to expanding immunotherapy benefits. Hence, exploration extended biomarker sources, such as tumor microenvironment, genomic markers, gut microbiota. studies introduced novel classification system, consensus molecular subtypes, aids identifying an immunogenic profile. These findings underscore necessity moving single toward comprehensive understanding immunological landscape CRC, facilitating development more effective, therapies.
Language: Английский
Citations
7
Critical Reviews in Oncology/Hematology, Journal Year: 2025, Volume and Issue: 208, P. 104629 - 104629
Published: Jan. 27, 2025
Language: Английский
Citations
0
Biomedicines, Journal Year: 2025, Volume and Issue: 13(3), P. 699 - 699
Published: March 12, 2025
Background/Objectives: Research on colorectal adenoma is significantly less comprehensive compared to studies carcinoma. Although a precursor of the majority sporadic cancers, not all adenomas develop into carcinomas. The complex interaction immune responses in premalignant tumor microenvironment might be factor for that. Methods: In this systematic review, we aim provide thorough analysis current research examining infiltration patterns tissues context cell-based, cytokine-based, and other immunological factor-related changes along conventional adenoma–carcinoma sequence. articles included review extend up December 2024 PubMed Web Science databases. Results: Most have shown significant differences cell counts, densities, cytokine expression levels associated with lesions (and/or cancer). No consensus immune-related tendencies concerning CD4+T cells CD8+T was reached. Decreasing mDCs plasma naïve B were detected ACS. increased density tissue eosinophils dramatically diminishes after transition As progresses, increasing IL-1α, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-21, IL-23, IL-33, TGF-β decreasing IL-12A, IL-18, IFN—γ, TNFα cytokines invasive carcinoma stage being detected. over-expression COX-2, PD-1/PD-L1, CTLA-4, ICOS/ICOSLG adenomatous cancerous also observed. Conclusions: Further are needed better understanding whole picture adenoma-associated immunity its impact precancerous lesion’s potential progress.
Language: Английский
Citations
0