ST6GAL1-mediated sialyl linkage switching in tumor-associated macrophages drives cancer-promoting nanotubes carrying α2,6-sialylation in anti-inflammatory cells DOI Open Access
Priya Dipta,

Naaz Bansal,

Zeynep Sumer‐Bayraktar

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 3, 2024

Abstract Tumor-associated macrophages (TAMs) form functionally diverse populations of innate immune cells in the tumor microenvironment (TME). Pro- and anti-inflammatory TAMs are central to cancer progression by shaping inflammation (im)balance, but it remains unknown if polarization-induced remodeling TAM glycocalyx critical for cellular communication occurs within TME. Taking a systems glycobiology approach, we here firstly used cell surface-focused glycomics lectin flow cytometry ex vivo polarized monocyte-derived demonstrate profound sialyl linkage switching surface N -glycome pro-inflammatory (α2,3-sialo-favored) (α2,6-sialo-dominant) macrophages. In contrast, no alterations sialylation were observed O -glycome. ST6GAL1 that modifies -glycans with α2,6-sialylation was elevated compared levels providing mechanistic basis switching, which supported silencing. Interestingly, SNA-focused cytochemistry revealed dense networks dynamic α2,6-sialylated protein-based nanotubules forming inter-connecting structures absent Temporal silencing caused nanotubule disintegration as evidenced SNA biotin fluorescence microscopy. Moreover, live recordings cultured without colorectal (CRC) showed reduced macrophage motility, attenuated inter-macrophage macrophage-CRC interactions diminished CRC proliferation upon disruption indicating functional roles nanotubules. Finally, recapitulated pro- from tissues patients advanced CRC. We report on consequences accompanying polarization.

Language: Английский

Immunosuppressive tumor microenvironment in the progression, metastasis, and therapy of hepatocellular carcinoma: from bench to bedside DOI Creative Commons
Yue Yin,

Weibo Feng,

Jie Chen

et al.

Experimental Hematology and Oncology, Journal Year: 2024, Volume and Issue: 13(1)

Published: Aug. 1, 2024

Abstract Hepatocellular carcinoma (HCC) is a highly heterogeneous malignancy with high incidence, recurrence, and metastasis rates. The emergence of immunotherapy has improved the treatment advanced HCC, but problems such as drug resistance immune-related adverse events still exist in clinical practice. immunosuppressive tumor microenvironment (TME) HCC restricts efficacy essential for progression metastasis. Therefore, it necessary to elucidate mechanisms behind TME develop apply immunotherapy. This review systematically summarizes pathogenesis formation TME, by which accelerates We also status further discuss existing challenges potential therapeutic strategies targeting TME. hope inspire optimizing innovating immunotherapeutic comprehensively understanding structure function HCC.

Language: Английский

Citations

20
Endothelial and Macrophage Interactions in the Angiogenic Niche. DOI
Fahad Hassan Shah, Heon‐Woo Lee

Cytokine & Growth Factor Reviews, Journal Year: 2024, Volume and Issue: 78, P. 64 - 76

Published: July 14, 2024

Language: Английский

Citations

5
Advances in the research of immunomodulatory mechanism of mesenchymal stromal/stem cells on periodontal tissue regeneration DOI Creative Commons

Dezhi Zhao,

Ruilin Yang,

Han-Xiao Wei

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 3, 2025

Periodontal disease is a highly prevalent worldwide that seriously affects people's oral health, including gingivitis and periodontitis. Although the current treatment of periodontal can achieve good control inflammation, it difficult to regenerate supporting tissues satisfactory therapeutic effect. In recent years, due tissue regeneration ability, research on Mesenchymal stromal/stem cells (MSCs) MSC-derived exosomes has been gradually deepened, especially its ability interact with microenvironment body in complex immunoregulatory network, which led many new perspectives strategies for diseases. This paper systematically reviews immunomodulatory (including bone immunomodulation) properties MSCs their role inflammatory microenvironment, summarizes pathways mechanisms by MSC-EVs have promoted lists potential areas future research, describes issues should be considered basic direction development "cell-free therapies" regeneration.

Language: Английский

Citations

0
Global Sensitivity Analysis of a Novel Signaling Network for Heart Growth With Local IGF1 Production DOI Creative Commons

Christian Bilas,

Claus Kratzer,

Arne Hinrichs

et al.

International Journal for Numerical Methods in Biomedical Engineering, Journal Year: 2025, Volume and Issue: 41(2)

Published: Feb. 1, 2025

Signaling networks can be used to describe the dynamic interplay of hormonal and mechanical factors that regulate heart growth. However, a qualitative analysis signaling is often difficult due their complexity nonlinear behavior. In this work, global sensitivity conducted determine most influential for growth over range model inputs. Furthermore, local production hormone insulin-like factor 1 (IGF1) in response high stretches as recently described by Zaman et al.(Immunity, 54, 2057) Wong 2072) incorporated. The computational results show increases influence stretch on significantly. Further key are hormones norepinephrine (NE), angiotensin II (AngII), globally produced IGF1 (g-IGF1). Our indicates novel consideration (l-IGF1) has considered

Language: Английский

Citations

0
Bacterial-Mediated In Situ Engineering of Tumour-Associated Macrophages for Cancer Immunotherapy DOI Open Access

Gabriela Christina Kuhl,

Mark Tangney

Cancers, Journal Year: 2025, Volume and Issue: 17(5), P. 723 - 723

Published: Feb. 20, 2025

Background/Objectives: Tumour-associated macrophages (TAMs) are critical components of the tumour microenvironment (TME), significantly influencing cancer progression and treatment resistance. This review aims to explore innovative use engineered bacteria reprogram TAMs, enhancing their anti-tumour functions improving therapeutic outcomes. Methods: We conducted a systematic following predefined protocol. Multiple databases were searched identify relevant studies on phenotypic plasticity, for reprogramming. Inclusion exclusion criteria applied select studies, data extracted using standardised forms. Data synthesis was performed summarise findings, focusing mechanisms benefits non-pathogenic modify TAMs. Results: The summarises findings that can selectively target promoting shift from tumour-promoting M2 phenotype tumour-fighting M1 phenotype. reprogramming enhances pro-inflammatory responses activity within TME. Evidence various indicates significant regression improved immune bacterial therapy. Conclusions: Reprogramming TAMs presents promising strategy approach leverages natural targeting abilities directly tumour, potentially patient outcomes offering new insights into immune-based treatments. Further research is needed optimise these methods assess clinical applicability.

Language: Английский

Citations

0
Post-translational modifications of immune checkpoints: unlocking new potentials in cancer immunotherapy DOI Creative Commons
Qiongjie Hu, Yueli Shi, Huang Wang

et al.

Experimental Hematology and Oncology, Journal Year: 2025, Volume and Issue: 14(1)

Published: March 14, 2025

Abstract Immunotherapy targeting immune checkpoints has gained traction across various cancer types in clinical settings due to its notable advantages. Despite this, the overall response rates among patients remain modest, alongside issues of drug resistance and adverse effects. Hence, there is a pressing need enhance checkpoint blockade (ICB) therapies. Post-translational modifications (PTMs) are crucial for protein functionality. Recent research emphasizes their pivotal role regulation, directly impacting expression function these key proteins. This review delves into influence significant PTMs—ubiquitination, phosphorylation, glycosylation—on signaling. By modifications, novel immunotherapeutic strategies have emerged, paving way advancements optimizing therapies future.

Language: Английский

Citations

0
Hepatic Nonparenchymal Cells and Liver-Associated Lymphoid Cells DOI
Carol R. Gardner, Jeffrey D. Laskin, Debra L. Laskin

et al.

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0
Macrophage Functions in Psoriasis: Lessons from Mouse Models DOI Open Access
Katarzyna Nazimek, Krzysztof Bryniarski

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(10), P. 5306 - 5306

Published: May 13, 2024

Psoriasis is a systemic autoimmune/autoinflammatory disease that can be well studied in established mouse models. Skin-resident macrophages are classified into epidermal Langerhans cells and dermal involved innate immunity, orchestration of adaptive maintenance tissue homeostasis due to their ability constantly shift phenotype adapt the current microenvironment. Consequently, both macrophage populations play dual roles psoriasis. In some circumstances, pro-inflammatory activated trigger psoriatic inflammation, while other cases anti-inflammatory stimulation results amelioration disease. These features make interesting candidates for modern therapeutic strategies. Owing significant progress knowledge, our review article summarizes achievements indicates future research directions better understand function

Language: Английский

Citations

3
Methylation and Transcriptomic Profiling Reveals Short Term and Long Term Regulatory Responses in Polarized Macrophages DOI Creative Commons
Giorgia Migliaccio, Jack Morikka, Giusy del Giudice

et al.

Computational and Structural Biotechnology Journal, Journal Year: 2024, Volume and Issue: 25, P. 143 - 152

Published: Aug. 17, 2024

Macrophage plasticity allows the adoption of distinct functional states in response to environmental cues. While unique transcriptomic profiles define these states, focusing solely on transcription neglects potential long-term effects. The investigation epigenetic changes can be used understand how temporary stimuli result lasting Epigenetic alterations play an important role pathophysiology macrophages, including their trained innate immunity, enabling faster and more efficient inflammatory responses upon subsequent encounters same pathogen or insult. In this study, we a multi-omics approach elucidate interplay between gene expression DNA-methylation, explore effects diverse polarizing environments macrophage activity. We identified common core set genes that are differentially methylated regardless exposure type, indicating fundamental mechanism for adaptation various stimuli. Functional analysis revealed processes requiring rapid displayed regulation, whereas functions critical adaptations exhibited co-regulation at both levels. Our study uncovers novel linked polarization. This discovery underscores epigenetics elucidating macrophages establish memory influence health outcomes.

Language: Английский

Citations

2
Function of alveolar macrophages in lung cancer microenvironment DOI Creative Commons
Takahiro Matsui,

Seiji Taniguchi,

Masaru Ishii

et al.

Inflammation and Regeneration, Journal Year: 2024, Volume and Issue: 44(1)

Published: May 8, 2024

Cancer tissues contain a wide variety of immune cells that play critical roles in suppressing or promoting tumor progression. Macrophages are one the most predominant populations microenvironment and composed two classes: infiltrating macrophages from bone marrow tissue-resident (TRMs). This review aimed to outline function TRMs microenvironment, focusing on lung cancer.

Language: Английский

Citations

0