NF-κB in biology and targeted therapy: new insights and translational implications

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: March 4, 2024

Abstract NF-κB signaling has been discovered for nearly 40 years. Initially, was identified as a pivotal pathway in mediating inflammatory responses. However, with extensive and in-depth investigations, researchers have that its role can be expanded to variety of mechanisms, biological processes, human diseases, treatment options. In this review, we first scrutinize the research process signaling, summarize composition, activation, regulatory mechanism signaling. We investigate interaction other important pathways, including PI3K/AKT, MAPK, JAK-STAT, TGF-β, Wnt, Notch, Hedgehog, TLR The physiological pathological states well intricate involvement inflammation, immune regulation, tumor microenvironment, are also explicated. Additionally, illustrate how is involved cancers, autoimmune cardiovascular metabolic neurological COVID-19. Further, discuss therapeutic approaches targeting IKK inhibitors, monoclonal antibodies, proteasome nuclear translocation DNA binding TKIs, non-coding RNAs, immunotherapy, CAR-T. Finally, provide an outlook field hope present stereoscopic, comprehensive will inform future clinical practice.

Language: Английский

---

The cancer-immunity cycle: Indication, genotype, and immunotype

Immunity, Journal Year: 2023, Volume and Issue: 56(10), P. 2188 - 2205

Published: Oct. 1, 2023

The cancer-immunity cycle provides a framework to understand the series of events that generate anti-cancer immune responses. It emphasizes iterative nature response where killing tumor cells by T initiates subsequent rounds antigen presentation and cell stimulation, maintaining active immunity adapting it evolution. Any step can become rate-limiting, rendering system unable control growth. Here, we update based on remarkable progress past decade. Understanding mechanism checkpoint inhibition has evolved, as our view dendritic in sustaining anti-tumor immunity. We additionally account for role microenvironment facilitating, not just suppressing, response, discuss importance considering tumor's immunological phenotype, "immunotype". While these new insights add some complexity cycle, they also provide targets research therapeutic intervention.

Language: Английский

---

Forks in the road for CAR T and CAR NK cell cancer therapies

Nature Immunology, Journal Year: 2023, Volume and Issue: 24(12), P. 1994 - 2007

Published: Nov. 27, 2023

Language: Английский

---

The promising role of tumor-associated macrophages in the treatment of cancer

Drug Resistance Updates, Journal Year: 2024, Volume and Issue: 73, P. 101041 - 101041

Published: Jan. 3, 2024

Language: Английский

---

Tumor initiation and early tumorigenesis: molecular mechanisms and interventional targets

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: June 18, 2024

Abstract Tumorigenesis is a multistep process, with oncogenic mutations in normal cell conferring clonal advantage as the initial event. However, despite pervasive somatic and expansion tissues, their transformation into cancer remains rare event, indicating presence of additional driver events for progression to an irreversible, highly heterogeneous, invasive lesion. Recently, researchers are emphasizing mechanisms environmental tumor risk factors epigenetic alterations that profoundly influencing early malignant evolution, independently inducing mutations. Additionally, evolution tumorigenesis reflects multifaceted interplay between cell-intrinsic identities various cell-extrinsic exert selective pressures either restrain uncontrolled proliferation or allow specific clones progress tumors. by which induce both intrinsic cellular competency remodel stress facilitate not fully understood. In this review, we summarize genetic, epigenetic, external events, effects on co-evolution transformed cells ecosystem during initiation evolution. A deeper understanding earliest molecular holds promise translational applications, predicting individuals at high-risk developing strategies intercept transformation.

Language: Английский

---

Identification of hypoxic macrophages in glioblastoma with therapeutic potential for vasculature normalization

Cancer Cell, Journal Year: 2024, Volume and Issue: 42(5), P. 815 - 832.e12

Published: April 18, 2024

Monocyte-derived tumor-associated macrophages (Mo-TAMs) intensively infiltrate diffuse gliomas with remarkable heterogeneity. Using single-cell transcriptomics, we chart a spatially resolved transcriptional landscape of Mo-TAMs across 51 patients isocitrate dehydrogenase (IDH)-wild-type glioblastomas or IDH-mutant gliomas. We characterize Mo-TAM subset that is localized to the peri-necrotic niche and skewed by hypoxic cues acquire hypoxia response signature. Hypoxia-TAM destabilizes endothelial adherens junctions activating adrenomedullin paracrine signaling, thereby stimulating hyperpermeable neovasculature hampers drug delivery in glioblastoma xenografts. Accordingly, genetic ablation pharmacological blockade produced restores vascular integrity, improves intratumoral concentration anti-tumor agent dabrafenib, achieves combinatorial therapeutic benefits. Increased proportion expression predictive tumor vessel hyperpermeability worse prognosis glioblastoma. Our findings highlight diversity spatial niche-steered reprogramming indicate potential therapeutics targeting normalize vasculature.

Language: Английский

---

Biomimetic Nano-Drug Delivery System: An Emerging Platform for Promoting Tumor Treatment

International Journal of Nanomedicine, Journal Year: 2024, Volume and Issue: Volume 19, P. 571 - 608

Published: Jan. 1, 2024

Abstract: With the development of nanotechnology, nanoparticles (NPs) have shown broad prospects as drug delivery vehicles. However, they exhibit certain limitations, including low biocompatibility, poor physiological stability, rapid clearance from body, and nonspecific targeting, which hampered their clinical application. Therefore, novel systems with improved biocompatibility high target specificity remains a major challenge. In recent years, biofilm mediated biomimetic nano-drug system (BNDDS) has become research hotspot focus in field life sciences. This new platform uses bio-nanotechnology to encapsulate synthetic NPswithin membrane, organically integrating immunogenicity, toxicity, tumor good adjustability versatility nanocarrier, shows promising applications precision therapy. this review, we systematically summarize progress BNDDS used for optimizing delivery, providing theoretical reference designing safe efficient treatment strategies improve outcomes. Keywords: nanoparticles, cell targeted therapy

Language: Английский

---

Macrophage-mediated myelin recycling fuels brain cancer malignancy

Cell, Journal Year: 2024, Volume and Issue: 187(19), P. 5336 - 5356.e30

Published: Aug. 12, 2024

Tumors growing in metabolically challenged environments, such as glioblastoma the brain, are particularly reliant on crosstalk with their tumor microenvironment (TME) to satisfy high energetic needs. To study intricacies of this metabolic interplay, we interrogated heterogeneity TME using single-cell and multi-omics analyses identified rewired tumor-associated macrophage (TAM) subpopulations pro-tumorigenic properties. These TAM subsets, termed lipid-laden macrophages (LLMs) reflect cholesterol accumulation, epigenetically rewired, display immunosuppressive features, enriched aggressive mesenchymal subtype. Engulfment cholesterol-rich myelin debris endows subsets TAMs acquire an LLM phenotype. Subsequently, LLMs directly transfer myelin-derived lipids cancer cells LXR/Abca1-dependent manner, thereby fueling heightened demands glioblastoma. Our work provides in-depth understanding immune-metabolic interplay during progression, laying a framework unveil targetable vulnerabilities

Language: Английский

---

Engineered CD47 protects T cells for enhanced antitumour immunity

Nature, Journal Year: 2024, Volume and Issue: 630(8016), P. 457 - 465

Published: May 15, 2024

Abstract Adoptively transferred T cells and agents designed to block the CD47–SIRPα axis are promising cancer therapeutics that activate distinct arms of immune system 1,2 . Here we administered anti-CD47 antibodies in combination with adoptively goal enhancing antitumour efficacy but observed abrogated therapeutic benefit due rapid macrophage-mediated clearance expressing chimeric antigen receptors (CARs) or engineered cell receptors. Anti-CD47-antibody-mediated CAR was potent enough serve as an effective safety switch. To overcome this challenge, CD47 variant CD47(Q31P) (47 E ), which engages SIRPα provides a ‘don’t eat me’ signal is not blocked by antibodies. TCR 47 resistant macrophages after treatment antibodies, mediate substantial, sustained macrophage recruitment tumour microenvironment. Although many recruited manifested M2-like profile 3 , combined therapy synergistically enhanced efficacy. Our study identifies major regulators persistence illustrates fundamental challenge combining T-cell-directed those macrophages. It delivers approach capable simultaneously harnessing effects macrophages, offering potency against solid tumours.

Language: Английский

---

Investigating the Dynamic Interplay Between Cellular Immunity and Tumor Cells in the Fight Against Cancer: An Updated Comprehensive Review

Iranian Journal of Blood and Cancer, Journal Year: 2024, Volume and Issue: 16(2), P. 84 - 101

Published: June 1, 2024

Language: Английский

---