CD9 expression

Here, we showed that CD9- BCP-ALL cells were preferentially resistant to prednisone and dexamethasone over other standard cytotoxic agents. Importantly, the MEK inhibitor trametinib exhibited higher synergy with GCs against CD9- than CD9+ lymphoblasts to reverse drug resistance in vitro and in vivo. Collectively, our results elucidate a previously unrecognized regulatory function of CD9 in GC sensitivity, and inform new strategies for management of children with resistant BCP-ALL.

Overexpression of CD9 due to hypoxic conditions leads to the activation of EGFR-signaling pathway resulting in cancer progression, resistance to chemotherapy. Hence, CD9 could be a potential target to suppress cancer progression.

We also summarize the potential role of Tspans as novel immunotherapy targets and as an approach to overcome drug resistance. Finally, we discuss the potential clinical value and therapeutic targets of Tspans in the treatments of digestive system malignancies and provide some guidance for future research.

We used a combination treatment strategy of cisplatin/etoposide plus GW4869 or Nexinhib20 on small cell lung cancer (SCLC) cell lines. We also found increased p53 and p21 expressions with western blot and significantly changing Bax, BCL2, caspase-3 and caspase-9 expressions. Inhibiting the exosome pathway offers opportunities for developing novel, effective treatment strategies for SCLC.

Rigorous research on potential enhancing factors, environmental or lifestyle, is crucial for its detection and prevention. The use of the reported profile for early risk stratification is suggested.

M-CSF secreted by gastric cancer cells can promote the proliferation, invasion and migration of gastric cancer cells by increasing the expression of SHP2 in TAMs.

The complexity of the phenotypic signature of lymphoblasts at diagnosis of B ALL is illustrated by the variability in the expression of LAP antigens. Knowledge of the expression levels of these markers in normal leukocytes and during normal B differentiation is crucial for an optimal interpretation of diagnostic cytometry results and serves as a basis for the biological follow-up of B ALL.

Multivariate analyses confirmed CD9 as an independent predictor of both events and relapse. The measurement of CD9 offers insights into patients necessitating intervention, warranting its seamless integration into the diagnostic marker panel to inform risk level and timely introduction of therapeutic intervention for childhood ALL.

EV surface expressions correlated with cytokine levels in pre-interventional HCC patients showed a CD4+ TH1 response, associated with CD44 expression. *Clinical Relevance/Application: EV surface expressions can be used as a prognostic parameter in MWA of HCC.

ConclusionDifferentially expressed non-neoplastic plasma EV subpopulations have significant clinical relevance in GBM including association with tumor volume and predicting survival. Validation of those markers in larger cohorts could reveal new prognostic biomarkers for GBM.

Ex vivo drug sensitivity profiling to prednisone (Pred) and dexamethasone (Dex) was performed on 6 BCP-ALL cell lines and 18 patient samples with differential CD9 expression. This study provides a definitive linkage of CD9 with GC sensitivity in childhood BCP-ALL mediated through a NR3C1-independent mechanism. CD9- cases could be prone to trametinib combination therapy, whereas CD9+ cases might need a third drug such as ruxolitinib to counteract GC resistance.

Exposure of CD9- AML cell lines (n=8) or samples (n=9) to the histone deacetylase inhibitor panobinostat significantly elevated CD9 mRNA and protein expression (3.1-32.2-fold, P<0.05), restored activating histone acetylation marks (4.1-41.6-fold, P<0.05), and potently suppressed myeloblast proliferation ex vivo (median IC50: 21.4 nM)...In NSG mice, co-transplantation of human PBMCs mounted an effective immunity against CD9+ but not CD9- AML (MV4-11 and MOLM-13, P<0.05), concomitant with a robust bone marrow infiltration of cytotoxic T cells. Taken together, our data provided molecular, cellular and clinical evidence showing the plausible function of CD9 as a key driver intertwining monocytic differentiation and immune recognition in pediatric AML, and inspired a new combinatorial epigenetic/immunotherapy for this rare but aggressive malignancy.

This is the largest study to evaluate the significance of CD9 in childhood ALL. We confirmed the results of our previous single-center study with this multicenter national study. CD9 positivity is definitively associated with a higher relapse probability particularly for patients with intermediate/high risk diseases, MRD positivity or specific cytogenetic background.

This work presents the composition of the CD9 protein web in BCP-ALL, revealing homogenous and heterogeneous partners across the leukemia subtypes. We also provide definitive evidence showing that CD9 binds to and regulates CD38 activity to mediate leukemia progression, representing the first universal protein partner being identified to have a functional consequence in BCP-ALL, thereby providing a mechanistic basis to support the development of CD9-targeted therapies for this life-threatening malignancy.

Our results identify an NK population susceptible sensitive to the fibrotic niche, a role for the IL27 and Rho signalling pathways in fibrosis-associated vascular remodelling and suggest a multi-cell-type source of extracellular matrix components. These results constitute the most extensive single-cell transcriptomic profiling of T-lymphocytes of human NASH.

CD9, CD63, and CD81 mRNA levels were high in RB tumors versus control retina, with increased and variable CD9 immunoreactivity in the invasive areas of the tumor. Serum sEVs could serve as a potential liquid biopsy source for understanding TR mechanisms in RB.

Overall, a CD4+ TH1 response, associated with CD44 expression was observed in pre- interventional HCC patients. Regarding the postinterventional phase, the underlying results suggest an activation of Treg cells in HCC and TH2 cells in NHCC patients.

Overall a poor rate of survival was observed in CD9 positive patients(p < 0.039). EGFR and p-Akt expression increased with increasing expression of CD9, suggesting its use as a biomarker to track the development of TSCC.

Importantly, CD9 knockdown or blockade sensitized SUM149 to JQ1 in vivo by trapping cells in the SCLED state and limiting transit to resistant cell states. Thus, CD9 appears to be critical for the transition from a SCLED state into treatment-resistant cell states and warrants exploration as a therapeutic target in basal-like breast cancer.

Here we report two AML patients with monocytic features that presented with relapsed/refractory (R/R) disease with no response either to transplant or navitoclax/venetoclax plus decitabine therapy. The first case has been transplanted; however, it relapsed 120 days post-transplant with a chimerism of 20%. The second case has shown R/R AML since the initial diagnosis. Additionally, the novel AVEN::NUTM1 fusion case reported in the literature, relapsed post-chemotherapy and was minimal residual disease positive 3 months after transplant with DNA sequencing detecting IDH1 and RUNX1 mutations.

Proteomic analysis will improve the cargo characterization of patient-EVs and potentially find other biomarkers. Further studies are needed to elucidate the role of EV subpopulations in immune response modulation in lung cancer.

According to in vitro and in vivo studies, tetraspanin CD9 is not clearly associated with either tumor suppression or promotion. Further mechanistic experiments will elucidate the role of CD9 in particular cancer types and specific conditions.

Systems prediction of Chronic Lung Allograft Dysfunction generated multiple fingerprints that enabled the development of predictors of CLAD. These results open the way to the integration of these fingerprints into a predictive handprint.

Significant changes of proteomic profile could be found in the urinary exosomes in the CRC patients. The differential expressed urinary exosomes derived proteins showed potential usage in diagnosis and prognosis of CRC.

Lastly, LYVE-1 and D2-40 allow an easier assessment of lymph vascular invasion, which can be considered a good predictor of SLN status. In conclusion, biomarkers to assess the lymph node status of cutaneous melanoma patients may play an important role in those cases where the clinician is in doubt whether or not to perform SLN biopsy.

CAF-derived exosomes, especially CD9-positive exosomes, have an inhibitory effect on the proliferation of malignant melanoma cells. These findings suggest that CD9 expression in CAFs is a promising prognostic marker for patients with malignant melanoma.

Mouse xenograft experiments indicate that HIF1α signaling pathway promotes ALL cells engraftment in a CD9-dependent manner. The present work increments our understanding of CD9 implication in ALL pathogenesis.

By using multiparametric flow cytometry, we confirmed the expansion of NK cells expressing CD9 immediately after autoHSCT, which exhibited higher granzyme B and perforin expression levels than CD9 NK cells. These results provide insights into the physiopathology of NK cells during their reconstitution after autoHSCT.

Our data strongly indicate that tetraspanin molecules play unexpected roles in the interaction of T cells with tumor, although further analysis is required. Finally, we hope that these findings would be useful for development of an effective personalized cancer immunotherapy in near future.

The cytotoxic agent doxorubicin (DOX)-loaded UEPP (UEPP-D) NPs with an initial particle size of 61.5 nm showed a burst release under acidic condition mimicking the tumor microenvironment...Finally, UEPP-D NPs showed a markedly higher antitumor efficacy and lower side-toxicity in MCF-7 tumor bearing nude mice model. Thus, this versatile nano-system with immune escape, homologous targeting, and rapid response release characteristics could be a promising tool for breast cancer treatment.

CB2 stimulation reduces the expression of CD9, SEC61G, TBX21, and TMSB4X genes involved in tumor growth and progression, and also negatively affects downstream intracellular pathways. Our findings suggest an antitumor role of CB2 stimulation in B-ALL, and highlight a functional correlation between CB2 receptors and specific anti-tumoral pathways, even though further investigations are needed.

Neoadjuvant chemotherapy endows CD9 with a significant prognostic value that differs between tumor and stromal areas in patients with pancreatic cancer.

The presence of CD9 hotspots could be essential for melanoma cell invasion in lymphatic and endothelial vessels. CD9 could be a valid prognostic factor for lymph node metastasis risk.

Exposure of CD9- AML cell lines (n=8) or samples (n=9) to panobinostat significantly elevated CD9 mRNA and protein expression (3.1-32.2-fold, P <0.05), and restored activating histone acetylation marks (4.1-41.6-fold, P <0.05)...In NSG mice, co-transplantation of human PBMCs mounted an effective immunity against CD9+ but not CD9- AML (MV4-11 and MOLM-13), concomitant with a robust bone marrow infiltration of cytotoxic T cells. Conclusion Our data provided molecular, cellular and clinical evidence showing the plausible function of CD9 as a key driver intertwining differentiation and immune recognition in pediatric AML, and inspired a new combinatorial epigenetic/immunotherapy for this rare but aggressive malignancy.

Exposure of CD9- AML cell lines (n = 8) or samples (n = 9) to a histone deacetylase inhibitor panobinostat significantly elevated CD9 mRNA and protein expression (3.1- to 32.2-fold, p < 0.05), restored activating histone acetylation marks (4.1- to 41.6-fold, p < 0.05), and potently suppressed myeloblast proliferation ex vivo (median IC50: 21.4 nM)...In NSG mice, co-transplantation of human PBMCs mounted an effective immunity against CD9+ but not CD9- AML (MV4-11 and MOLM-13), concomitant with a robust bone marrow infiltration of cytotoxic T cells. Taken together, our data provided molecular, cellular and clinical evidence showing the plausible function of CD9 as a key driver intertwining differentiation and immune recognition in paediatric AML, and inspired a new combinatorial epigenetic/immunotherapy for this rare but aggressive malignancy.

Histological samples from uterine pregnancies, including decidual stromal cells, showed increased SCF mRNA expression, mast cell numbers and LIF mRNA expression thereof compared with tubal pregnancy. SCF produced by decidual stromal cells enhanced the migration and LIF production of mast cells, and promoted the migration and differentiation of trophoblasts to increase the likelihood of successful human pregnancy.

CD9 protein expression was downregulated in PCa, compared to BPH, while CD63 protein expression was upregulated in high-grade PCa but downregulated in low-grade PCa. CD63 protein upregulation, CD9 downregulation, and loss of MMR protein characterized the shorter PFS of high-grade PCa patients. CD9, CD63, and MMR could be the routine immunohistochemical biomarkers for the diagnosis and risk stratification of PCa.

In conclusion, these results showed that declined expression of CD9 was associated with poor survival in human solid tumors. CD9 may be a valuable prognostic predictive biomarker and a potential therapeutic target in human solid tumors.

CD9 antigen expression in the exosomes of the oral epithelium explained the intercellular flow of SolCD44 and other fluids in the leukoplakia area. We conclude that the OncAlert Oral Cancer Rapid test is a valuable screening method in daily clinical practice, in terms of complementing clinical diagnostics methods and to assess the potential for early malignancy.

Flow cytometric evaluation of expression of selected antigens can be used for fast identification of markers of aneuploidy in pediatric BCP-ALL, before genetic tests results are available. Understanding the biological significance of aneuploidy in leukemia can potentially be exploited therapeutically using targeted therapies against specific blast cell subclones.