CCR5 Proinflammatory Allele in Prostate Cancer Risk

Balistreri, Carmela Rita; Carruba, Giuseppe; Calabrò, Maurizio; Campisi, Ildegarda; Carlo, Daniele Di; Lio, Domenico; Colonna‐Romano, Giuseppina; Candore, Giuseppina; Caruso, Calogero

doi:10.1111/j.1749-6632.2008.03691.x

Cited by 28 publications

(8 citation statements)

References 19 publications

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“…Another chemokine receptor CCR5, which is expressed on a broad spectrum of immune cells ( 84 ), interacts with its ligands CCL3, CCL4, and CCL5 ( 89 ). Interestingly, the patients with a mutated CCR5 variant were reported to be resistant to the prostate cancer development ( 90 ). Furthermore, CCR5 has a critical role in tumor progression since it has been shown that the CCR5–CCL5 axis supported tumor growth, invasion, and migration of MDSC to the tumor site ( 87 , 91 ).…”

Section: Blocking Mdsc Traffickingmentioning

confidence: 99%

Targeting Myeloid-Derived Suppressor Cells to Bypass Tumor-Induced Immunosuppression

et al. 2018

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The immune system has many sophisticated mechanisms to balance an extensive immune response. Distinct immunosuppressive cells could protect from excessive tissue damage and autoimmune disorders. Tumor cells take an advantage of those immunosuppressive mechanisms and establish a strongly immunosuppressive tumor microenvironment (TME), which inhibits antitumor immune responses, supporting the disease progression. Myeloid-derived suppressor cells (MDSC) play a crucial role in this immunosuppressive TME. Those cells represent a heterogeneous population of immature myeloid cells with a strong immunosuppressive potential. They inhibit an antitumor reactivity of T cells and NK cells. Furthermore, they promote angiogenesis, establish pre-metastatic niches, and recruit other immunosuppressive cells such as regulatory T cells. Accumulating evidences demonstrated that the enrichment and activation of MDSC correlated with tumor progression, recurrence, and negative clinical outcome. In the last few years, various preclinical studies and clinical trials targeting MDSC showed promising results. In this review, we discuss different therapeutic approaches on MDSC targeting to overcome immunosuppressive TME and enhance the efficiency of current tumor immunotherapies.

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Section: Blocking Mdsc Traffickingmentioning

confidence: 99%

Targeting Myeloid-Derived Suppressor Cells to Bypass Tumor-Induced Immunosuppression

et al. 2018

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“…Individuals with a functional mutation in CCR5 (deletion of the N-terminal 32 nucleotides) display a high state of HIV resistance (63). Later, it was found that they also show low prevalence of cancer diseases, particularly cancer of the prostate (64). This motivated us to explore the underlying mechanism by which the absence of CCR5 confers cancer resistance.…”

Section: The Recruitment Of Mdsc At Tumor Sites As a Multistep Event mentioning

confidence: 99%

The Development and Homing of Myeloid-Derived Suppressor Cells: From a Two-Stage Model to a Multistep Narrative

Karin

2020

Front. Immunol.

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Myeloid-derived suppressor cells (MDSC) represent a heterogeneous population of immature myeloid cells. Under normal conditions, they differentiate into macrophages, dendritic cells, and granulocytes. Under pathological conditions, such as chronic inflammation, or cancer, they tend to maintain their immature state as immature myeloid cells that, within the tumor microenvironment, become suppressor cells and assist tumor escape from immune eradication. MDSC are comprised of two major subsets: monocytic MDSC (M-MDSC) and polymorphonuclear MDSC (PMN-MDSC). Monocytic myeloid cells give rise to monocytic cells, whereas PMN-MDSC share similarities with neutrophils. Based on their biological activities, a two-stage model that includes the mobilization of the periphery as myeloid cells and their activation within the tumor microenvironment converting them into suppressor cells was previously suggested by D. Gabrilovich. From the migratory viewpoint, we are suggesting a more complex setup. It starts with crosstalk between the tumor site and the hematopoietic stem and progenitor cells (HSPCs) at the bone marrow (BM) and secondary lymphatic organs, resulting in rapid myelopoiesis followed by mobilization to the blood. Although myelopoiesis is coordinated by several cytokines and transcription factors, mobilization is selectively directed by chemokine receptors and may differ between M-MDSC and PMN-MDSC. These myeloid cells may then undergo further expansion at these secondary lymphatic organs and then home to the tumor site. Finally, selective homing of T cell subsets has been associated with retention at the target organs directed by adhesion molecules or chemokine receptors. The possible relevance to myeloid cells is still speculative but is discussed.

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“…Hence, our results demonstrated, for the first time, a role of Glo2 in prostate tumorigenesis as well as suggesting a possible mechanism. Both genetic and environmental factors participate in PCa pathogenesis [ 121 , 122 ]. Nevertheless, the molecular biology and mechanisms of prostate carcinogenesis remain to be further elucidated in order to identify additional diagnostic factors.…”

Section: Prostate Cancer (Pca)mentioning

confidence: 99%

Glyoxalases in Urological Malignancies

Antognelli

Talesa

2018

IJMS

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Urological cancers include a spectrum of malignancies affecting organs of the reproductive and/or urinary systems, such as prostate, kidney, bladder, and testis. Despite improved primary prevention, detection and treatment, urological cancers are still characterized by an increasing incidence and mortality worldwide. While advances have been made towards understanding the molecular bases of these diseases, a complete understanding of the pathological mechanisms remains an unmet research goal that is essential for defining safer pharmacological therapies and prognostic factors, especially for the metastatic stage of these malignancies for which no effective therapies are currently being used. Glyoxalases, consisting of glyoxalase 1 (Glo1) and glyoxalase 2 (Glo2), are enzymes that catalyze the glutathione-dependent metabolism of cytotoxic methylglyoxal (MG), thus protecting against cellular damage and apoptosis. They are generally overexpressed in numerous cancers as a survival strategy by providing a safeguard through enhancement of MG detoxification. Increasing evidence suggests that glyoxalases, especially Glo1, play an important role in the initiation and progression of urological malignancies. In this review, we highlight the critical role of glyoxalases as regulators of tumorigenesis in the prostate through modulation of various critical signaling pathways, and provide an overview of the current knowledge on glyoxalases in bladder, kidney and testis cancers. We also discuss the promise and challenges for Glo1 inhibitors as future anti-prostate cancer (PCa) therapeutics and the potential of glyoxalases as biomarkers for PCa diagnosis.

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CCR5 Proinflammatory Allele in Prostate Cancer Risk

Cited by 28 publications

References 19 publications

Targeting Myeloid-Derived Suppressor Cells to Bypass Tumor-Induced Immunosuppression

Targeting Myeloid-Derived Suppressor Cells to Bypass Tumor-Induced Immunosuppression

The Development and Homing of Myeloid-Derived Suppressor Cells: From a Two-Stage Model to a Multistep Narrative

Glyoxalases in Urological Malignancies

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