Modulation of Tumor-Associated Macrophages to Overcome Immune Suppression in the Hepatocellular Carcinoma Microenvironment

Cancers, Journal Year: 2024, Volume and Issue: 17(1), P. 66 - 66

Published: Dec. 29, 2024

Hepatocellular carcinoma (HCC) is a major global health issue characterized by poor prognosis and complex tumor biology. One of the critical components HCC microenvironment (TME) tumor-associated macrophages (TAMs), which play pivotal role in modulating growth, immune evasion, metastasis. Macrophages are divided into two subtypes: pro-inflammatory M1 anti-inflammatory M2, both may exist TME with altered function proportion. The M2 further subdivided four distinct suppressive subsets. TAMs generally counted as M2-like functions that exert significant influence on cancer progression ability tumors to escape surveillance. Their involvement responses via different mechanisms at local systemic levels has made them key target for therapeutic interventions seeking enhance treatment outcomes. How TAMs’ depletion influences primary interest immunotherapies. purpose this review delve recent progress TAM-targeting therapies. We will explore current theories, benefits, challenges associated or inhibition. manuscript concludes future directions potential implications clinical practice.

Language: Английский

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Relationship between Epithelial-to-Mesenchymal Transition and Tumor-Associated Macrophages in Colorectal Liver Metastases

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(24), P. 16197 - 16197

Published: Dec. 19, 2022

The liver is the most common metastatic site in colorectal cancer (CRC) patients. Indeed, 25–30% of cases develop metastasis (CLM), showing an extremely poor 5-year survival rate and resistance to conventional anticancer therapies. Tumor-associated macrophages (TAMs) provide a nurturing microenvironment for CRC metastasis, promoting epithelial-to-mesenchymal transition (EMT) through TGF-β signaling pathway, thus driving tumor cells acquire mesenchymal properties that allow them migrate from primary invade new site. EMT known contribute disruption blood vessel integrity generation circulating (CTCs), being closely related high potential numerous solid cancers. Despite fact it well-recognized crosstalk between inflammatory crucial process, association role TAMs still poorly understood. In this review, we elaborated on exert induction during CLM development. Since are major source liver, also focused novel insights into their TGF-β-induced EMT.

Language: Английский

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Understanding the Dual Role of Macrophages in Tumor Growth and Therapy: A Mechanistic Review

Chemistry & Biodiversity, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 27, 2025

ABSTRACT Macrophages are heterogeneous cells that the mediators of tissue homeostasis. These immune originated from monocytes and classified into two basic categories, M1 M2 macrophages. macrophages exhibit anti‐tumorous inflammatory reactions due to behavior phagocytosis. or tumor‐associated (TAMs) most abundant in tumor microenvironment (TME) have a role progression by interacting with other TME. By expression various cytokines, chemokines, growth factors, TAMs lead strengthening cell proliferation, angiogenesis, suppression system which further support invasion metastasis. This review discusses recent updated mechanisms regarding Moreover, current therapeutic approaches targeting TAMs, their advantages, limitations also summarized, treatment outlined along an elaboration regression comprehensive article possibly helps understand underlying comparative way level advanced one.

Language: Английский

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Targeted nanomedicine for reprogramming the tumor innate immune system: From bench to bedside

European Journal of Pharmaceutics and Biopharmaceutics, Journal Year: 2024, Volume and Issue: 204, P. 114510 - 114510

Published: Sept. 21, 2024

Language: Английский

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Surgical stress-induced tumor immune suppressive environment

Carcinogenesis, Journal Year: 2024, Volume and Issue: 45(4), P. 185 - 198

Published: Feb. 15, 2024

Abstract Despite significant advances in cancer treatment over the decades, surgical resection remains a prominent management approach for solid neoplasms. Unfortunately, accumulating evidence suggests that stress caused by tumor may potentially trigger postoperative metastatic niche formation. Surgical not only activates sympathetic-adrenomedullary axis and hypothalamic–pituitary–adrenocortical but also induces hypoxia hypercoagulable state. These adverse factors can negatively impact immune system downregulating effector cells upregulating suppressor cells, which contribute to colonization progression of niche. This review summarizes effects on four types (neutrophils, macrophages, natural killer cytotoxic T lymphocytes) two immunosuppressive (regulatory myeloid-derived cells), discusses mechanisms relapse progression. Additionally, relevant therapeutic strategies minimize pro-tumorigenic are elucidated.

Language: Английский

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Remodeling tumor microenvironment using pH-sensitive biomimetic co-delivery of TRAIL/R848 liposomes against colorectal cancer

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics, Journal Year: 2024, Volume and Issue: 0(0), P. 1 - 10

Published: Jan. 1, 2024

Background: Despite significant advancements in the development of anticancer therapies over past few decades, clinical management colorectal cancer remains a challenging task.This study aims to investigate inhibitory effects cancer-targeting liposomes against cancer.Materials and Methods: Liposomes consisting 3β-[N-(N′, N′-dimethylamino ethane)carbamoyl]-cholesterol (DC-CHOL), cholesterol (CHOL), dioleoylphosphatidylethanolamine (DOPE) at molar ratio 1:1:0.5 were created used as carriers deliver an apoptosis-inducing plasmid encoding tumor necrosis factor-related ligand (pTRAIL) gene, along with toll-like receptor (TLR7) agonist Rsiquimod (R848).The rationale behind this design is that pTRAIL can trigger cell apoptosis by activating DR4/5 receptor, while R848 stimulate immune microenvironment.Results: Experimental results demonstrated synergistic encapsulated (RTL) suppressing proliferation cells.Moreover, further vivo investigations revealed strong anti-tumor efficacy RTL xenograft orthotropic situ models cancer.Conclusions: These findings collectively highlight therapeutic potential R848/pTRAIL-loaded treatment cancer.

Language: Английский

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Marine-Derived Therapeutics for the Management of Glioblastoma: A Case Series and Comprehensive Review of the Literature

Onco, Journal Year: 2024, Volume and Issue: 4(4), P. 369 - 380

Published: Nov. 4, 2024

Introduction: Glioblastoma is a fatal intracranial neoplasm that refractory to treatment, with inevitable disease recurrence and progression death. Marine-derived compounds, including those found in nutraceutical products, may provide therapeutic benefit the setting of glioblastoma. We present two patient cases whose courses demonstrate compelling role for marine-derived products management Cases: Case 1 describes MGMT promoter unmethylated glioblastoma who went on complete standard care chemoradiation along concurrent use majority sea cucumber (MSC) blend known as SeaCare® (SeaCare, Torrington, CT, USA). Her survival over 2 years significantly exceeds recognized median time complicated course experienced dramatic improvement after initiation MSC blend, an exceptional 4 post-diagnosis. Discussion: The mechanisms underlie these clinical effects are likely multifaceted but hinge modification tumor immune microenvironment suppression tumorigenic effects. Specifically, change tumor-associated macrophages (TAMs) within central this complex interplay. Conclusions: Ultimately, marine treatment novel promising strategy warrants further investigation.

Language: Английский

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SpottedPy quantifies relationships between spatial transcriptomic hotspots and uncovers environmental cues of epithelial-mesenchymal plasticity in breast cancer

Genome biology, Journal Year: 2024, Volume and Issue: 25(1)

Published: Nov. 11, 2024

Spatial transcriptomics is revolutionizing the exploration of intratissue heterogeneity in cancer, yet capturing cellular niches and their spatial relationships remains challenging. We introduce SpottedPy, a Python package designed to identify tumor hotspots map interactions within cancer ecosystem. Using we examine epithelial-mesenchymal plasticity breast highlight stable associated with angiogenic hypoxic regions, shielded by CAFs macrophages. Hybrid mesenchymal hotspot distribution follows transformation gradients reflecting progressive immunosuppression. Our method offers flexibility explore at different scales, from immediate neighbors broader tissue modules, providing new insights into microenvironment dynamics.

Language: Английский

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Natural compounds modulate the mechanism of action of tumour-associated macrophages against colorectal cancer: a review

Journal of Cancer Research and Clinical Oncology, Journal Year: 2024, Volume and Issue: 150(11)

Published: Nov. 15, 2024

Colorectal cancer (CRC) exhibits a substantial morbidity and mortality rate, with its aetiology pathogenesis remain elusive. It holds significant importance within the tumour microenvironment (TME) exerts crucial regulatory influence on tumorigenesis, progression, metastasis. TAMs possess capability to foster CRC pathogenesis, proliferation, invasion, metastasis, as well angiogenesis, immune evasion, resistance. Furthermore, can mediate prognosis of CRC. In this paper, we review mechanisms by which natural compounds target exert anti-CRC effects from perspective promotional CRC, mainly regulating polarization TAMs, reducing infiltration recruitment enhancing phagocytosis macrophages, signalling pathways cytokines, discuss potential value therapeutic strategies compounds-targeting pathway in clinical treatment.

Language: Английский

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Immune evasion by cancer stem cells ensures tumor initiation and failure of immunotherapy

Exploration of Immunology, Journal Year: 2023, Volume and Issue: unknown, P. 384 - 405

Published: Aug. 31, 2023

Cancer stem cells (CSCs) are a small subpopulation of that drive the formation and progression tumors. However, during tumor initiation, how CSCs communicate with neighbouring immune to overcome powerful surveillance barrier in order form, spread, maintain tumor, remains poorly understood. It is, therefore, absolutely necessary understand number tumor-initiating (TICs) survive attack (a) “elimination phase” “tumor immune-editing”, (b) establishment regional or distant after metastasis, (c) recurrence therapy. Mounting evidence suggests suppress system through variety distinct mechanisms ensure survival not only but also non-stem cancer (NSCCs), which eventually form mass. In this review article, via change landscape tissue origin, contains macrophages, dendritic (DCs), myeloid-derived suppressor (MDSCs), natural killer (NK) cells, tumor-infiltrating lymphocytes, favour tumorigenesis were discussed. The failure immunotherapy might be explained by such interaction between cells. This will shed light on critical role evasion emphasize importance CSC-targeted as cutting-edge technique for battling restricting communication CSCs.

Language: Английский

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