The dual-function chemokine receptor CCR2 drives migration and chemokine scavenging through distinct mechanisms DOI
Thomas M. Shroka, Irina Kufareva,

Catherina L. Salanga

et al.

Science Signaling, Journal Year: 2023, Volume and Issue: 16(770)

Published: Jan. 31, 2023

C-C chemokine receptor 2 (CCR2) is a dual-function receptor. Similar to other G protein-coupled receptors, it promotes monocyte infiltration into tissues in response the CCL2, and, like atypical receptors (ACKRs), scavenges from extracellular environment. CCR2 therefore mediates CCL2-dependent signaling as (GPCR) and also limits CCL2 scavenger We investigated mechanisms underlying scavenging, including involvement of intracellular proteins typically associated with GPCR internalization. Using CRISPR knockout cell lines, we showed that scavenged by constitutively internalizing remove space recycling back surface for further rounds ligand sequestration. This process occurred independently proteins, kinases (GRKs), β-arrestins, clathrin, which distinct "professional" couple GRKs, or both. These findings set stage understanding molecular regulators determine scavenging may have implications drug development targeting this therapeutically important

Language: Английский

Role of the CCL2-CCR2 axis in cardiovascular disease: Pathogenesis and clinical implications DOI Creative Commons
Haixia Zhang, Ke Yang, Feng Chen

et al.

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Aug. 30, 2022

The CCL2-CCR2 axis is one of the major chemokine signaling pathways that has received special attention because its function in development and progression cardiovascular disease. Numerous investigations have been performed over past decades to explore Laboratory data on for disease shown satisfactory outcomes, yet clinical translation remains challenging. In this article, we describe mechanisms action evolution diseases including heart failure, atherosclerosis coronary atherosclerotic disease, hypertension myocardial use pathway as a targeted therapy are summarized. potential treatment explored.

Language: Английский

Citations

84
Functional Roles of Chemokine Receptor CCR2 and Its Ligands in Liver Disease DOI Creative Commons
Shaoping She, Liying Ren, Pu Chen

et al.

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Feb. 25, 2022

Chemokines are a family of cytokines that orchestrate the migration and positioning immune cells within tissues critical for function system. CCR2 participates in liver pathology, including acute injury, chronic hepatitis, fibrosis/cirrhosis, tumor progression, by mediating recruitment to inflammation sites. Although variety chemokines have been well studied various diseases, there is no comprehensive review presenting roles all known chemokine ligands (CCL2, CCL7, CCL8, CCL12, CCL13, CCL16, PSMP) disease, this aims fill gap. The introduction each includes its discovery, corresponding chemotactic receptors, physiological functions tumors, impact on different cell subgroups.

Language: Английский

Citations

76
CXCL12-CXCR4/CXCR7 Axis in Cancer: from Mechanisms to Clinical Applications DOI Creative Commons
Yaru Yang, Jiayan Li,

Wangrui Lei

et al.

International Journal of Biological Sciences, Journal Year: 2023, Volume and Issue: 19(11), P. 3341 - 3359

Published: Jan. 1, 2023

Cancer is a multi-step disease caused by the accumulation of genetic mutations and/or epigenetic changes, and biggest challenge around world.Cytokines, including chemokines, exhibit expression changes disorders in all human cancers.These cytokine abnormalities can disrupt homeostasis immune function, make outstanding contributions to various stages cancer development such as invasion, metastasis, angiogenesis.Chemokines are superfamily small molecule chemoattractive cytokines that mediate variety cellular functions.Importantly, interactions chemokine members CXCL12 its receptors CXCR4 CXCR7 have broad impact on tumor cell proliferation, survival, angiogenesis, microenvironment, thus participate onset many cancers leukemia, breast cancer, lung prostate multiple myeloma.Therefore, this review aims summarize latest research progress future challenges regarding role CXCL12-CXCR4/CXCR7 signaling axis highlights potential biomarker or therapeutic target for providing essential strategies novel targeted therapies.

Language: Английский

Citations

70
S100A8 and S100A9 in Cancer DOI
Yu Chen,

Yuzhen Ouyang,

Zhixin Li

et al.

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2023, Volume and Issue: 1878(3), P. 188891 - 188891

Published: March 29, 2023

Language: Английский

Citations

69
Targeting cytokine and chemokine signaling pathways for cancer therapy DOI Creative Commons
Ming Yi, Tianye Li,

Mengke Niu

et al.

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

Published: July 22, 2024

Abstract Cytokines are critical in regulating immune responses and cellular behavior, playing dual roles both normal physiology the pathology of diseases such as cancer. These molecules, including interleukins, interferons, tumor necrosis factors, chemokines, growth factors like TGF-β, VEGF, EGF, can promote or inhibit growth, influence microenvironment, impact efficacy cancer treatments. Recent advances targeting these pathways have shown promising therapeutic potential, offering new strategies to modulate system, progression, overcome resistance conventional therapies. In this review, we summarized current understanding implications cytokine chemokine signaling By exploring molecules biology response, highlighted development novel agents aimed at modulating combat The review elaborated on nature cytokines promoters suppressors tumorigenesis, depending context, discussed challenges opportunities presents for intervention. We also examined latest advancements targeted therapies, monoclonal antibodies, bispecific receptor inhibitors, fusion proteins, engineered variants, their metastasis, microenvironment. Additionally, evaluated potential combining therapies with other treatment modalities improve patient outcomes. Besides, focused ongoing research clinical trials that pivotal advancing our application cytokine- chemokine-targeted patients.

Language: Английский

Citations

64
Deciphering the performance of macrophages in tumour microenvironment: a call for precision immunotherapy DOI Creative Commons
Belén Toledo,

Linrui Zhu Chen,

María Paniagua-Sancho

et al.

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: June 11, 2024

Abstract Macrophages infiltrating tumour tissues or residing in the microenvironment of solid tumours are known as tumour-associated macrophages (TAMs). These specialized immune cells play crucial roles growth, angiogenesis, regulation, metastasis, and chemoresistance. TAMs encompass various subpopulations, primarily classified into M1 M2 subtypes based on their differentiation activities. macrophages, characterized by a pro-inflammatory phenotype, exert anti-tumoural effects, while with an anti-inflammatory function protumoural regulators. highly versatile respond to stimuli from other constituents within (TME), such growth factors, cytokines, chemokines, enzymes. induce polarization towards one phenotype another, leading complex interactions TME components influencing both pro-tumour anti-tumour processes. This review comprehensively deeply covers literature origin well intricate interplay between TME, dual nature promoting pro- Moreover, delves primary pathways implicated macrophage polarization, examining diverse that regulate this process. role shaping functions macrophages. In addition, advantages limitations current clinical interventions reviewed, including enhancing TAM phagocytosis, inducing exhaustion, inhibiting recruitment, polarizing M1-like phenotype. conclusion, treatment strategies targeting precision medicine show promise, overcoming several obstacles is still necessary achieve accessible efficient immunotherapy.

Language: Английский

Citations

50
Pre-metastatic niche: formation, characteristics and therapeutic implication DOI Creative Commons
Yuhang Wang,

Jiachi Jia,

Fuqi Wang

et al.

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

Published: Sept. 25, 2024

Language: Английский

Citations

22
Development of pharmacological immunoregulatory anti-cancer therapeutics: current mechanistic studies and clinical opportunities DOI Creative Commons
Nanhao Yin, Xintong Li, Xuanwei Zhang

et al.

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

Published: May 22, 2024

Abstract Immunotherapy represented by anti-PD-(L)1 and anti-CTLA-4 inhibitors has revolutionized cancer treatment, but challenges related to resistance toxicity still remain. Due the advancement of immuno-oncology, an increasing number novel immunoregulatory targets mechanisms are being revealed, with relevant therapies promising improve clinical immunotherapy in foreseeable future. Therefore, comprehending larger picture is important. In this review, we analyze summarize current landscape preclinical translational mechanistic research, drug development, trials that brought about next-generation pharmacological anti-cancer agents candidates beyond classical immune checkpoint inhibitors. Along further clarification immunobiology advances antibody engineering, targeting additional inhibitory checkpoints, including LAG-3, TIM-3, TIGIT, CD47, B7 family members becoming important part research discovery, as structurally functionally optimized agonists co-stimulatory molecules T cells. Exemplified bispecific cell engagers, newly emerging bi-specific multi-specific antibodies can provide considerable benefits. Next-generation also include epigenetic drugs cytokine-based therapeutics. Cell therapies, vaccines, oncolytic viruses not covered review. This comprehensive review might aid development fastest possible adoption effective immuno-oncology modalities for benefit patients.

Language: Английский

Citations

20
The Cytokine Network in Colorectal Cancer: Implications for New Treatment Strategies DOI Creative Commons

Heidi Braumüller,

Bernhard Mauerer,

J.C. Andri�s

et al.

Cells, Journal Year: 2022, Volume and Issue: 12(1), P. 138 - 138

Published: Dec. 29, 2022

Colorectal cancer (CRC) is one of the most frequent tumor entities worldwide with only limited therapeutic options. CRC not a genetic disease several mutations in specific oncogenes and/or suppressor genes such as APC, KRAS, PIC3CA, BRAF, SMAD4 or TP53 but also multifactorial including environmental factors. Cancer cells communicate their environment mostly via soluble factors cytokines, chemokines growth to generate favorable microenvironment (TME). The TME, heterogeneous population differentiated and progenitor cells, plays critical role regulating development, growth, invasion, metastasis therapy resistance. In this context, cytokines from TME influence each other, eliciting an inflammatory milieu that can either enhance suppress metastasis. Additionally, lines evidence exist composition microbiota regulates processes, controlled by cytokine secretion, play carcinogenesis progression. review, we discuss networks between microbiome colorectal related treatment strategies, goal cytokine-mediated strategies could overcome common resistance tumors.

Language: Английский

Citations

44
Targeting macrophages: a novel treatment strategy in solid tumors DOI Creative Commons
Mengmeng Liu, Lina Liu, Yongping Song

et al.

Journal of Translational Medicine, Journal Year: 2022, Volume and Issue: 20(1)

Published: Dec. 12, 2022

In the tumor microenvironment (TME), tumor-associated macrophages (TAMs) are most abundant immune cells, which act as a key regulator in tumorigenesis and progression. Increasing evidence have demonstrated that TME alters nature of to maintain dynamic tissue homeostasis, allowing TAMs acquire ability stimulate angiogenesis, promote metastasis recurrence, suppress anti-tumor responses. Furthermore, tumors with high TAM infiltration poor prognoses resistant treatment. field solid tumor, exploration tumor-promoting mechanisms has attracted much attention targeting emerged promising immunotherapeutic strategy. Currently, common therapeutic options for follows: deletion TAMs, inhibition recruitment, release phagocytosis by reprogramming remodel their capacity. Promisingly, study chimeric antigen receptor (CAR-Ms) may provide even greater benefit patients tumors. this review, we discuss how progression well summarize emerging strategies macrophages.

Language: Английский

Citations

41