CCR5 expression

Maraviroc treatment did not affect OC cell viability, but strongly potentiated the antiproliferative activity, apoptosis induction, cell cycle blockage, DNA damage, and ROS formation by trabectedin. In A2780cis cisplatin-resistant cells, the cross-resistance to trabectedin was overcame by the combination with maraviroc. Maraviroc enhanced trabectedin cytotoxicity in OC 3Dimensional spheroids and THP-1-monocytes. Both maraviroc and trabectedin interact with drug efflux pump MDR1/P-gp, overexpressed in recurrent OC patients. Maraviroc increased trabectedin intracellular accumulation and the MDR1-inhibitor verapamil, like maraviroc, increased trabectedin cytotoxicity. In OC tumor xenografts the combination with maraviroc further reduced tumor growth, angiogenesis, and monocyte infiltration by trabectedin. In conclusion, this study offers a preclinical rationale for the use of maraviroc as new option to improve trabectedin activity in relapsed chemoresistant OC patients.

Our data show a strong association between CCR5/CCL5 gene expression and distinct molecular features, gene expression profiles, TME cell infiltration, and treatment benefit in CRC. Targeting the CCR5/CCL5 axis may have clinical applications in selected CRC subgroups and may play a key role in developing and deploying strategies to modulate the immune TME for CRC treatment.

Moreover, we found that the tumor-promotive role of CCL5 is dependent on activation of the JAK2/STAT3 signaling pathway. CCL5 may play an oncogenic role in BC and may also serve as a potential diagnostic and prognostic biomarker.

Paclitaxel leads to peripheral neuropathy (paclitaxel-induced peripheral neuropathy [PIPN]) in approximately 50% of cancer patients. Consistent with this, administration of CCR5 antagonist maraviroc suppresses the development of neuropathic nociception. These results implicate gut microbiota/bile acids/CCR5 signaling in the induction of PIPN, thus suggesting a target for PIPN treatment.

The effects of CCR5 antagonists in OSCC have been poorly studied, and this study reports in vitro and in vivo evidence for the effects of Maraviroc in OSCC. Our results suggest that the CCR5/CCL5 axis plays a role in oral cancer behavior, and that its inhibition is a promising new therapy alternative.

Further analysis revealed that TLR8 and CCR5 expression increased responsiveness to immunotherapy by promoting M0 macrophage and memory B cell infiltration of LUAD tissues. In patients with LUAD, TLR8 and CCR5 expression are potential markers of a favorable response to combined immunotherapy and RT.

Compared with haplotype H1 rs2227010-rs2734648-rs1799987-rs1799988-rs1800023-rs1800024: A-T-G-T-G-C, haplotype H5: A-G-G-T-G-C increased the risk of NSCLC by over 10-fold (p < .0001, OR = 16.09, 95%CI: 5.37-48.20, adjusted by sex and age) and notably depressed the transcriptional activity of the CCR5 promoter in 293T, A549, H1299 and HeLa cells. In conclusion, CCR5 promoter polymorphisms are significantly associated with NSCLC by affecting the transcriptional activity of the CCR5 promoter.

The HCM vaccine results in significant anti-tumor efficacy in murine syngeneic murine glioma which is dependent on upregulation of CCL4 in the TME driven by CD4 T cells. The CCL4 exerts its effect through microglia expressing CCR5 in the TME. Further analysis of the effects of vaccination on microglia phenotype and function are underway.

The HCM vaccine results in significant anti-tumor efficacy in murine syngeneic murine glioma which is dependent on upregulation of CCL4 in the TME driven by CD4 T cells. The CCL4 exerts its effect through microglia expressing CCR5 in the TME. Further analysis of the effects of vaccination on microglia phenotype and function are underway.

Inhibitors of CCR5 (CCR5i), either small molecules (maraviroc, vicriviroc) or humanized monoclonal antibodies (leronlimab) have shown anti-tumor and anti-metastatic properties in preclinical studies. In early clinical studies, reviewed herein, CCR5i have shown promising results and evidence for effects on both the tumor and the anti-tumor immune response. Current clinical studies have therefore included combination therapy approaches with checkpoint inhibitors.

Although changes in inflammatory cells can partly be attributed to the larger sample size of operation specimens, the differences also mirror a true change in the tumor microenvironment. The changes in inflammatory cells could be partly due to the need to restrict excess inflammation at the site of the biopsy.

Nevertheless, at the clinical forefront of CRISPR-HIV technology, more efforts should be directed to advance nonhuman primate (NHP) models for studies of HIV pathogenesis and off-target assessments within this system. CRISPR-Cas9 knock out of host HSCT-expressing CCR5 or CXCR4 may confer HIV-resistance, which when applied to bedside therapeutics in an allogeneic or autologous manner can warrant a permanent and effective treatment outcome.

The aim of this paper is to observe the effects of X-ray irradiation and C-C chemokine receptor 5 (CCR5) antagonist (maraviroc) on hepatocellular carcinoma (HCC) in an orthotopic mouse model... Scientific data analysis revealed the therapeutic effectiveness of calycopterin in the medicine for the treatment of human hepatoblastoma cancer.

This study made the foundation for future studies evaluating HIV-1 cross-species infection in a murine animal model. The results provided new direction for studies investigating the development of vaccines, antiviral drugs screening, and HIV/AIDS pathogenesis.

Exploratory endpoints include changes in intratumoral biomarkers (CTLs, PDL1, chemokines) in pre- and post-treatment peripheral tumor biopsies and immune changes in the blood. Clinical trial information: NCT04348747.

CCL5 is a ligand for the CC motif receptor 5 (CCR5), for which a clinically approved inhibitor exists, namely Maraviroc...High CCL5 or CCR5 expression is associated with worse prognosis in low grade esophageal carcinomas. Implications: These data highlight the role of CCL5 in tumorigenesis and the therapeutic potential of targeting the CCL5-CCR5 axis in ESCC.

Our major findings are that the frequency of pTFH cells, but not pTFR cells was higher in HIV-infected participants of the MACS and that pTFH cells expressed less CCR5 in HIV-infected MACS participants. Constitutive expression of CCR5 in TFR cells supports their potential to contribute to HIV persistence.

The expression levels of CCR5 can affect the prognosis of patients with ovarian cancer. CT-based radiomics could serve as a new tool for prognosis prediction.

CCL3-CCR5 interaction promotes cell migration and invasiveness, and functions as a prognostic biomarker for COAD.

Vorinostat treatment of patient-derived metastatic PNET tissues augmented recruitment of autologous T cells, which was substantiated in a mouse model of PNET. Pharmacologic induction of chemokine expression may represent a promising approach for enhancing the immunogenicity of metastatic PNET TMEs.

CCR5 expressed activated Treg cells increased in peripheral blood, accumulated more in tumor sites of HCC patients possibly through CCR5-CCL5 interaction.CCR5 + aTreg could predicted patients’ overall survival in our cohort and validated by TCGA data. In addition, imatinib could decrease the inhibition ability of aTreg. These result implied immunotherapy targeted at these aTreg cells may be promising.

High expression of CCR5 plays an important prognostic role in HNSC patients and may serve as a prognostic biomarker correlated with immune infiltration, and further studies are still needed to investigate therapeutic targeting HNSC patients in the future.

The expression level was correlated with the clinical stage and nerve invasion. The expression of chemokine CCL3 and receptor CCR5 was positively correlated with the expression of TRAF6 and NF-κB and could promote the proliferation, invasion, and migration of colorectal cancer cells through TRAF6 and NF-κB.

We identified novel ferroptosis-related genes with clinical value in glioma and revealed their possible tumor immune relevance. Furthermore, in glioma, we pinpointed underlying critical elements of the chemokine, immune microenvironment and immune checkpoint, and were able to develop a predictive model of prognosis.

Thus, these multiple dysregulated chemokine receptors could represent novel clinical markers as diagnostic and prognostic tools. Moreover, this study highlights the relevance of chemokine signaling crosstalk in the tumor microenvironment of aggressive lymphomas.

Glioma cells remodel the immune microenvironment through the high expression of CCR5 and lead to a poor prognosis in patients with LGG. The inhibition of CCR5 may contribute to the efficacy of LGG immunotherapy.

Despite advances in immunotherapy, the standard treatment consists of chemotherapy combining pemetrexed and cisplatin. These results also underline the potential involvement of changes in tumor microenvironment in resistance to chemotherapy via the recruitment of CCR5+ M2 macrophages. Furthermore, in vivo treatment with Maraviroc significantly decreased the growth of resistant tumors which reinforces our initial hypothesis.

Blocking cytokine-receptor axes may reverse TEX. Our finding provides novel insights into TEX in COVID-19 and new clues for cytokine-targeted immunotherapy development.

In conclusion, this study identified four potential genetic markers associated with HCC immunity and assessed their association with HCC patient's prognosis and immune microenvironment. The study results are expected to provide theoretical guidance for immunotherapy of HCC patients.

Using a liquid biopsy approach, we evaluated two populations of tumor-associated cells emanating from primary tumors, with data suggesting that upregulation of the motility chemokine CCR5 in TACs provides clinically relevant opportunities for treating and tracking drug targetable receptors in mBC.

Overall, our results suggest that a distinct chemokine receptor pattern might be associated with early pro- gression of FL. Thus, several receptors might serve as a useful clinical prognostic marker for risk stratification and might be potential novel therapeutic targets in future lymphoma therapy.

Our data indicate that a distinct CR expres- sion pattern is implicated in the development of PCNS-L and that several receptors might serve as a useful clinical prognostic marker and represent a potential novel therapeutic target for lymphoma therapy.

Our study demonstrates that T cell recruitment toward mPNET tissue is dependent upon CCR5 expression. These results reveal that PNET TME is regulatable by vorinostat and opens an avenue of potential sensitization to immune checkpoint blockade among patients with PNETs.

Early results of this on-going study demonstrate the detection of circulating CCR2+CCR5+ MO-MDSCs in the preoperative whole blood of NSCLC patients compared to healthy controls. Resection of the tumor is associated with a decrease of these MO-MDSCs after treatment. We are evaluating if any increase in CCR2+CCR5+ MO-MDSC in long term will allow us to use it as an adjuvant tool along with CT monitoring as a biomarker of residual or recurrent disease.

We also demonstrated that FCER1G and co-expressed genes in TME were related to the aggregation of leukocytes via pathway analysis. By analyzing the eQTL from the cancer genome using germline variants and TME-based RNA sequencing, we identified the eQTL in immune response genes that impact colorectal cancer characteristics and survival.

4. The study unveiled a protective target against CRC.

Patient was initiated on therapy with daratumumab, lenalidomide, and dexamethasone on day+33. Additionally, HIV plasma loads remained undetected while on Highly Active Antiretroviral Therapy which is to continue for at least one-year post transplant. Daratumumab could a potential therapy in rituximab refractory HIV infected patients in the post allo-HSCT setting

Therefore, O-GlcNAcylation of Blimp-1 in lymphocytes may serve as a new target for the treatment of metastatic breast cancer. Implications: This study reveals a new mechanism by which the lymphatic system promotes breast cancer cell metastasis.

Moreover, aspects of chronic infection were already present at early stages in this experimental model. Collectively, we suggest that HTLV-1 infection modulates host immune responses to favor viral persistence.