The Role of Chemokine Receptor CXCR3 and Its Ligands in Renal Cell Carcinoma

Gudowska-Sawczuk, Monika; Kudelski, Jacek; Mroczko, Barbara

doi:10.3390/ijms21228582

Cited by 23 publications

(15 citation statements)

References 56 publications

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“…As mentioned above, CXCL10 is responsible for, inter alia, stimulation of monocytes or NK cells, migration of T lymphocytes, or modulation of the expression of adhesion molecules [ 51 , 52 ]. At the same time, it is known that CXCL10 or CRP-stimulated monocytes produce IL-6.…”

Section: Resultsmentioning

confidence: 99%

What Is Currently Known about the Role of CXCL10 in SARS-CoV-2 Infection?

Gudowska-Sawczuk

Mroczko

2022

IJMS

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Dysregulation of the immune response plays an important role in the progression of SARS-CoV-2 infection. A “cytokine storm”, which is a phenomenon associated with uncontrolled production of large amounts of cytokines, very often affects patients with COVID-19. Elevated activity of chemotactic cytokines, called chemokines, can lead to serious consequences. CXCL10 has an ability to activate its receptor CXCR3, predominantly expressed on macrophages, T lymphocytes, dendritic cells, natural killer cells, and B cells. So, it has been suggested that the chemokine CXCL10, through CXCR3, is associated with inflammatory diseases and may be involved in the development of COVID-19. Therefore, in this review paper, we focus on the role of CXCL10 overactivity in the pathogenesis of COVID-19. We performed an extensive literature search for our investigation using the MEDLINE/PubMed database. Increased concentrations of CXCL10 were observed in COVID-19. Elevated levels of CXCL10 were reported to be associated with a severe course and disease progression. Published studies revealed that CXCL10 may be a very good predictive biomarker of patient outcome in COVID-19, and that markedly elevated CXCL10 levels are connected with ARDS and neurological complications. It has been observed that an effective treatment for SARS-CoV-2 leads to inhibition of “cytokine storm”, as well as reduction of CXCL10 concentrations. It seems that modulation of the CXCL10–CXCR3 axis may be an effective therapeutic target of COVID-19. This review describes the potential role of CXCL10 in the pathogenesis of COVID-19, as well as its potential immune–therapeutic significance. However, future studies should aim to confirm the prognostic, clinical, and therapeutic role of CXCL10 in SARS-CoV-2 infection.

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Section: Resultsmentioning

confidence: 99%

What Is Currently Known about the Role of CXCL10 in SARS-CoV-2 Infection?

Gudowska-Sawczuk

Mroczko

2022

IJMS

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“…Examples of these are prostate cancer, thyroid, colon cancer, and glioblastoma [ 26 ]. CXC-type chemokine receptor 3 (CXCR3) is reported to be an important biomarker for the invasive subtype of kidney cancer, renal cell carcinoma [ 27 ]. On the other hand, CXC-type chemokine receptor 7 (CXCR7), activated by aaptamine, is widely expressed in different organs including the bone marrow, liver, heart, kidney, thymus, stomach, lymph nodes, pituitary gland, and brain [ 28 ].…”

Section: Resultsmentioning

confidence: 99%

GPCR Pharmacological Profiling of Aaptamine from the Philippine Sponge Stylissa sp. Extends Its Therapeutic Potential for Noncommunicable Diseases

Luyao

Luesch

2021

Molecules

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We report the first isolation of the alkaloid aaptamine from the Philippine marine sponge Stylissa sp. Aaptamine possessed weak antiproliferative activity against HCT116 colon cancer cells and inhibited the proteasome in vitro at 50 µM. These activities may be functionally linked. Due to its known, more potent activity on certain G-protein coupled receptors (GPCRs), including α-adrenergic and δ-opioid receptors, the compound was profiled more broadly at sub-growth inhibitory concentrations against a panel of 168 GPCRs to potentially reveal additional targets and therapeutic opportunities. GPCRs represent the largest class of drug targets. The primary screen at 20 µM using the β-arrestin functional assay identified the antagonist, agonist, and potentiators of agonist activity of aaptamine. Dose-response analysis validated the α-adrenoreceptor antagonist activity of aaptamine (ADRA2C, IC50 11.9 µM) and revealed the even more potent antagonism of the β-adrenoreceptor (ADRB2, IC50 0.20 µM) and dopamine receptor D4 (DRD4, IC50 6.9 µM). Additionally, aaptamine showed agonist activity on selected chemokine receptors, by itself (CXCR7, EC50 6.2 µM; CCR1, EC50 11.8 µM) or as a potentiator of agonist activity (CXCR3, EC50 31.8 µM; CCR3, EC50 16.2 µM). These GPCRs play a critical role in the treatment of cardiovascular disease, diabetes, cancer, and neurological disorders. The results of this study may thus provide novel preventive and therapeutic strategies for noncommunicable diseases (NCDs).

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“… 316 In lung and renal cell carcinoma models, intratumoral injection of CXCL9 or CXCL10 proteins, respectively, reduced neovascularization and delayed tumor growth by inducing tumor‐infiltrating CXCR3 + monocytes. 317 , 318 Additionally, a novel CXCL10 fusion protein (IP10‐scFv) coadministered with CTLs successfully induced tumor‐infiltrating lymphocytes and prolonged survival in mice. 319 CXCL11 is a controversial target for cancer treatment because it helps induce Tregs migration.…”

Section: Different Chemokine Axesmentioning

confidence: 99%

“…In contrast, reducing CXCL9 and CXCL10 expression in animal models significantly decreased the efficacy of anti‐PD‐1 drugs and limited the aggregation of CD8 + T cells within the TME 316 . In lung and renal cell carcinoma models, intratumoral injection of CXCL9 or CXCL10 proteins, respectively, reduced neovascularization and delayed tumor growth by inducing tumor‐infiltrating CXCR3 + monocytes 317,318 . Additionally, a novel CXCL10 fusion protein (IP10‐scFv) coadministered with CTLs successfully induced tumor‐infiltrating lymphocytes and prolonged survival in mice 319 .…”

Section: Different Chemokine Axesmentioning

confidence: 99%

Role of chemokine systems in cancer and inflammatory diseases

Zhao

2022

MedComm

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Chemokines are a large family of small secreted proteins that have fundamental roles in organ development, normal physiology, and immune responses upon binding to their corresponding receptors. The primary functions of chemokines are to coordinate and recruit immune cells to and from tissues and to participate in regulating interactions between immune cells. In addition to the generally recognized antimicrobial immunity, the chemokine/chemokine receptor axis also exerts a tumorigenic function in many different cancer models and is involved in the formation of immunosuppressive and protective tumor microenvironment (TME), making them potential prognostic markers for various hematologic and solid tumors. In fact, apart from its vital role in tumors, almost all inflammatory diseases involve chemokines and their receptors in one way or another. Modulating the expression of chemokines and/or their corresponding receptors on tumor cells or immune cells provides the basis for the exploitation of new drugs for clinical evaluation in the treatment of related diseases. Here, we summarize recent advances of chemokine systems in protumor and antitumor immune responses and discuss the prevailing understanding of how the chemokine system operates in inflammatory diseases. In this review, we also emphatically highlight the complexity of the chemokine system and explore its potential to guide the treatment of cancer and inflammatory diseases.

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The Role of Chemokine Receptor CXCR3 and Its Ligands in Renal Cell Carcinoma

Cited by 23 publications

References 56 publications

What Is Currently Known about the Role of CXCL10 in SARS-CoV-2 Infection?

What Is Currently Known about the Role of CXCL10 in SARS-CoV-2 Infection?

GPCR Pharmacological Profiling of Aaptamine from the Philippine Sponge Stylissa sp. Extends Its Therapeutic Potential for Noncommunicable Diseases

Role of chemokine systems in cancer and inflammatory diseases

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