PD-L1/miR-155 Interplay in Pediatric High-Grade Glioma

Litak, Jakub; Grajkowska, Wiesława; Bogucki, Jacek; Kowalczyk, Paweł; Petniak, Alicja; Podkowiński, Arkadiusz; Szumiło, Justyna; Kocki, Janusz; Roliński, Jacek; Rahnama-Hezavah, Mansur; Roszkowski, Marcin; Grochowski, Cezary

doi:10.3390/brainsci12030324

Cited by 3 publications

(2 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CUR effectively suppressed the IFN-γ-triggered elevation of PD-L1 by impeding STAT1 phosphorylation, thereby furnishing a mechanistic elucidation for its modulation of PD-L1 in melanoma cells [ 47 ]. On the contrary, a significant positive correlation was found between the miR-155 concentration and the extent of PD-L1 expression in melanoma, breast cancer, glioma and B cell lymphomas tumor tissue [ 13 , 18 , 48 – 50 ]. CUR/miR155@DssD-Hb NPs induced higher expression of PD-L1 compared to CUR@DssD-Hb NPs, implying its potential in harnessing the efficacy of immune checkpoint blockade (ICB) therapy [ 18 ].…”

Section: Resultsmentioning

confidence: 99%

Reactive oxygen species/glutathione dual sensitive nanoparticles with encapsulation of miR155 and curcumin for synergized cancer immunotherapy

Li,

Wang,

Xie

et al. 2024

J Nanobiotechnol

View full text Add to dashboard Cite

Considerable attention has been directed towards exploring the potential efficacy of miR-155 in the realm of cancer immunotherapy. Elevated levels of miR-155 in dendritic cells (DCs) have been shown to enhance their maturation, migration, cytokine secretion, and their ability to promote T cell activation. In addition, overexpression of mir155 in M2 macrophages boost the polarization towards the M1 phenotype. Conversely, miR-155 has the propensity to induce the accumulation of immunosuppressive cells like regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) in the tumor tissue. To account for this discrepancy, it is imperative to get help from a drug that could deal with immunosuppressive effect. Curcumin (CUR) exhibits the capacity to prompt Tregs converse into T helper 1 cells, fostering the polarization of M2 tumor-associated macrophage towards the M1 phenotype, and impeding the recruitment and aggregation of MDSCs within the tumor microenvironment. Nonetheless, CUR is known to exert an immunosuppressive impact on DCs by hindering the expression of maturation markers, cytokines, and chemokines, thereby prevent DCs response to immunostimulatory agents. Hence, a reactive oxygen species/glutathione dual responsive drug conveyance platform (CUR/miR155@DssD-Hb NPs) was devised to co-deliver CUR and miR155, with the aim of exploring their synergistic potential in bolstering a sustained and robust anti-tumor immune response. In vitro and in vivo results have suggested that CUR/miR155@DssD-Hb NPs can effectively inhibit the viability of 4T1 and B16F10 tumor cells, trigger the release of damage associated molecular patterns, stimulate DCs maturation, subsequent activation of CD8+ T cells, diminish immunosuppressive cell populations (MDSCs, Tregs, M2 TAMs and exhausted T cells), promote the formation of long-term immunity and lessen the formation of metastatic nodules in the lungs. In summary, the co-delivery system integrating CUR and miR155 (CUR/miR155@DssD-Hb NPs) demonstrates promise as a promising strategy for the immunotherapy of melanoma and triple negative breast cancer. Graphical abstract

show abstract

Section: Resultsmentioning

confidence: 99%

Reactive oxygen species/glutathione dual sensitive nanoparticles with encapsulation of miR155 and curcumin for synergized cancer immunotherapy

Li,

Wang,

Xie

et al. 2024

J Nanobiotechnol

View full text Add to dashboard Cite

show abstract

“…Additionally, the study discovered a strong association between the concentration of miR-155 and the expression level of PD-L1 in tumor tissue of high-grade pediatric glioma (p-HGG) [ 154 ].…”

Section: Micrornas: Bridging the Gap Between Gene Regulation Immune C...mentioning

confidence: 99%

MicroRNAs as regulators of immune checkpoints in cancer immunotherapy: targeting PD-1/PD-L1 and CTLA-4 pathways

Zabeti Touchaei,

Vahidi

2024

Cancer Cell Int

View full text Add to dashboard Cite

Immunotherapy has revolutionized cancer treatment by harnessing the power of the immune system to eliminate tumors. Immune checkpoint inhibitors (ICIs) block negative regulatory signals that prevent T cells from attacking cancer cells. Two key ICIs target the PD-1/PD-L1 pathway, which includes programmed death-ligand 1 (PD-L1) and its receptor programmed death 1 (PD-1). Another ICI targets cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). While ICIs have demonstrated remarkable efficacy in various malignancies, only a subset of patients respond favorably. MicroRNAs (miRNAs), small non-coding RNAs that regulate gene expression, play a crucial role in modulating immune checkpoints, including PD-1/PD-L1 and CTLA-4. This review summarizes the latest advancements in immunotherapy, highlighting the therapeutic potential of targeting PD-1/PD-L1 and CTLA-4 immune checkpoints and the regulatory role of miRNAs in modulating these pathways. Consequently, understanding the complex interplay between miRNAs and immune checkpoints is essential for developing more effective and personalized immunotherapy strategies for cancer treatment. Graphical Abstract

show abstract

Elucidating the impact of parthanatos-related microRNAs on the tumoral immune microenvironment and clinical outcome in low-grade gliomas

Zhu,

Wu,

Zheng

et al. 2024

Discov Onc

View full text Add to dashboard Cite

Parthanatos, a cell death mechanism triggered by PARP-1 activation, is implicated in oncogenic processes, yet their role in low-grade gliomas (LGG) remains poorly understood. This research investigates Parthanatos-related miRNAs' prognostic and immunomodulatory potential, alongside their influence on therapeutic outcomes in LGGs. Comprehensive miRNA and mRNA profiles of LGG patients were extracted from TCGA and CGGA databases, integrating clinical parameters to identify Parthanatos-associated miRNAs. IHC data validated the expression levels of Parthanatos-related genes in glioma versus normal brain tissues. Protein–protein interaction networks and Spearman correlation analysis facilitated the identification of key miRNAs. Parthanatos-related miRNA indices (PMI) were screened using Lasso and assessed for their accuracy in predicting prognosis, comparing their associated potential molecular functions and heterogeneity of the immune microenvironment. Drug sensitivity was assessed between different groups and optimal therapeutic agents were predicted. Validate the expression levels of key miRNAs by qPCR. Ninety-one miRNAs significantly associated with Parthanatos were screened, through which a PMI prognosis model of nine miRNAs was constructed. The PMI score was able to independently predict the prognosis of patients with LGG, and the nomogram constructed based on the PMI provided a practical tool for clinical prediction of patient prognosis. The proportion of immune response was lower in patients in the high-risk group, and there were significant differences in drug sensitivity between different risk classes, while drugs such as Fasudil were identified as the most promising therapeutic agents for patients in the high-risk group. Our findings highlight the critical role of Parthanatos-associated miRNAs in the progression and treatment of LGG, offering novel insights into their prognostic value and therapeutic potential.

show abstract

PD-L1/miR-155 Interplay in Pediatric High-Grade Glioma

Cited by 3 publications

References 41 publications

Reactive oxygen species/glutathione dual sensitive nanoparticles with encapsulation of miR155 and curcumin for synergized cancer immunotherapy

Reactive oxygen species/glutathione dual sensitive nanoparticles with encapsulation of miR155 and curcumin for synergized cancer immunotherapy

MicroRNAs as regulators of immune checkpoints in cancer immunotherapy: targeting PD-1/PD-L1 and CTLA-4 pathways

Elucidating the impact of parthanatos-related microRNAs on the tumoral immune microenvironment and clinical outcome in low-grade gliomas

Contact Info

Product

Resources

About