Downregulation of A2AR by siRNA loaded PEG-chitosan-lactate nanoparticles restores the T cell mediated anti-tumor responses through blockage of PKA/CREB signaling pathway

Masjedi, Ali; Hassannia, Hadi; Atyabi, Fatemeh; Rastegari, Ali; Hojjat‐Farsangi, Mohammad; Namdar, Afshin; Soleimanpour, Hassan; Azizi, Gholamreza; Nikkhoo, Afshin; Ghalamfarsa, Ghasem; Mirshafiey, Abbas; Jadidi‐Niaragh, Farhad

doi:10.1016/j.ijbiomac.2019.03.223

Cited by 61 publications

(33 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, blockage of these checkpoint molecules and/or their ligands may be considered as a promising therapeutic strategy to restore anti‐tumor effects of T cells in the tumor microenvironment. We have demonstrated that the blockage of CD73 and adenosine A2a receptor increases the anti‐tumor potential of DC vaccines and restores T‐cell responses in tumor‐bearing mice . We have also shown that inhibition of hypoxia‐inducible factor‐1 α or adenosine receptor might enhance the efficacy of DC vaccine in animal models .…”

Section: Introductionmentioning

confidence: 87%

“…We have demonstrated that the blockage of CD73 and adenosine A2a receptor increases the anti-tumor potential of DC vaccines and restores T-cell responses in tumorbearing mice. [6][7][8] We have also shown that inhibition of hypoxia-inducible factor-1a or adenosine receptor might enhance the efficacy of DC vaccine in animal models. 9 These results imply that the attenuation of an immunosuppressive tumor microenvironment may increase the function of DC vaccine, followed by tumor elimination.…”

Section: Introductionmentioning

confidence: 91%

“…Briefly, 400 ll CDS NPs loaded with 10 lg siRNA molecules were mixed with 200 ll fetal bovine serum and gently shaken at 37°. Twenty-microliter samples were then collected at predetermined times (2,6,12,18,24, and 36 hr), and stored at À20°for subsequent analysis by gel electrophoresis.…”

Section: Validation and Characterization Of The Cds Npsmentioning

confidence: 99%

See 2 more Smart Citations

Blockage of immune checkpoint molecules increases T‐cell priming potential of dendritic cell vaccine

et al. 2019

Self Cite

View full text Add to dashboard Cite

Summary Dendritic cell (DC) ‐based cancer immunotherapy is one of the most important anti‐cancer immunotherapies, and has been associated with variable efficiencies in different cancer types. It is well‐known that tumor microenvironment plays a key role in the efficacy of various immunotherapies such as DC vaccine. Accordingly, the expression of programmed death ligand 1 (PD‐L1) on DCs, which interacts with PD‐1 on T cells, leads to inhibition of anti‐tumor responses following presentation of tumor antigens by DCs to T cells. Therefore, we hypothesized that down‐regulation of PD‐L1 in DCs in association with silencing of PD‐1 on T cells may lead to the enhancement of T‐cell priming by DCs to have efficient anti‐tumor T‐cell responses. In this study, we silenced the expression of PD‐L1 in DCs and programmed cell death protein 1 (PD‐1) in T cells by small interfering RNA (siRNA) ‐loaded chitosan–dextran sulfate nanoparticles (NPs) and evaluated the DC phenotypic and functional characteristics and T‐cell functions following tumor antigen recognition on DCs, ex vivo. Our results showed that synthesized NPs had good physicochemical characteristics (size 77·5 nm and zeta potential of 14·3) that were associated with efficient cellular uptake and target gene silencing. Moreover, PD‐L1 silencing was associated with stimulatory characteristics of DCs. On the other hand, presentation of tumor antigens by PD‐L1‐negative DCs to PD‐1‐silenced T cells led to induction of potent T‐cell responses. Our findings imply that PD‐L1‐silenced DCs can be considered as a potent immunotherapeutic approach in combination with PD‐1‐siRNA loaded NPs, however; further in vivo investigation is required in animal models.

show abstract

Section: Introductionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 91%

See 1 more Smart Citation

Blockage of immune checkpoint molecules increases T‐cell priming potential of dendritic cell vaccine

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…There are several trials on approaches involving a combination of CD38 with anti-PD-1 that have been found to stimulate enhanced antitumor responses by T cell-mediated by enhanced Granzyme B and IFN-γ expression by CD8 + T cells. 79 , 264 , 285 Findings from another study showed that A 2A R cells had enhanced the penetration in hypoxic tumors. 286 Although the focus of most of the combination approaches indicates the possibility of ADO targeting aimed at enhancing T cell responses, ADO axis targeting, including NK cells, can enhance other immune subsets comprised in the TME.…”

Section: Study and Progress Of Adenosine In The Nk Cell Cancer Immunomentioning

confidence: 99%

Immune checkpoint molecules in natural killer cells as potential targets for cancer immunotherapy

Cao

Wang

Jin

et al. 2020

Sig Transduct Target Ther

100

View full text Add to dashboard Cite

Recent studies have demonstrated the potential of natural killer (NK) cells in immunotherapy to treat multiple types of cancer. NK cells are innate lymphoid cells that play essential roles in tumor surveillance and control that efficiently kill the tumor and do not require the major histocompatibility complex. The discovery of the NK’s potential as a promising therapeutic target for cancer is a relief to oncologists as they face the challenge of increased chemo-resistant cancers. NK cells show great potential against solid and hematologic tumors and have progressively shown promise as a therapeutic target for cancer immunotherapy. The effector role of these cells is reliant on the balance of inhibitory and activating signals. Understanding the role of various immune checkpoint molecules in the exhaustion and impairment of NK cells when their inhibitory receptors are excessively expressed is particularly important in cancer immunotherapy studies and clinical implementation. Emerging immune checkpoint receptors and molecules have been found to mediate NK cell dysfunction in the tumor microenvironment; this has brought up the need to explore further additional NK cell-related immune checkpoints that may be exploited to enhance the immune response to refractory cancers. Accordingly, this review will focus on the recent findings concerning the roles of immune checkpoint molecules and receptors in the regulation of NK cell function, as well as their potential application in tumor immunotherapy.

show abstract

“…Adenosine A2a receptor (A2aR) is highly expressed by astrocytes and microglia and contributes significantly to neuroinflammatory and neuromodulator processes (Orr et al, 2015 ; Zhao et al, 2017 ; Masjedi et al, 2019 ). Many neurodegenerative diseases including HIV, AD and TBI involve chronic neuroinflammation thereby increasing the risk for regional accumulation of pTau, tau oligomers and neurofibrillary tangles contributing to neurocognitive dysfunction.…”

Section: Aqp4 Dysregulation Adenosine A2a Receptor and Neurodegeneramentioning

confidence: 99%

Astrocytes, HIV and the Glymphatic System: A Disease of Disrupted Waste Management?

Tice¹,

McDevitt

Langford³

2020

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

The discovery of the glial-lymphatic or glymphatic fluid clearance pathway in the rodent brain led researchers to search for a parallel system in humans and to question the implications of this pathway in neurodegenerative diseases. Magnetic resonance imaging studies revealed that several features of the glymphatic system may be present in humans. In both rodents and humans, this pathway promotes the exchange of interstitial fluid (ISF) and cerebrospinal fluid (CSF) through the arterial perivascular spaces into the brain parenchyma. This process is facilitated in part by aquaporin-4 (AQP4) water channels located primarily on astrocytic end feet that abut cerebral endothelial cells of the blood brain barrier. Decreased expression or mislocalization of AQP4 from astrocytic end feet results in decreased interstitial flow, thereby, promoting accumulation of extracellular waste products like hyperphosphorylated Tau (pTau). Accumulation of pTau is a neuropathological hallmark in Alzheimer's disease (AD) and is accompanied by mislocalization of APQ4 from astrocyte end feet to the cell body. HIV infection shares many neuropathological characteristics with AD. Similar to AD, HIV infection of the CNS contributes to abnormal aging with altered AQP4 localization, accumulation of pTau and chronic neuroinflammation. Up to 30% of people with HIV (PWH) suffer from HIV-associated neurocognitive disorders (HAND), and changes in AQP4 may be clinically important as a contributor to cognitive disturbances. In this review, we provide an overview and discussion of the potential contributions of NeuroHIV to glymphatic system functions by focusing on astrocytes and AQP4. Although HAND encompasses a wide range of neurocognitive impairments and levels of neuroinflammation vary among and within PWH, the potential contribution of disruption in AQP4 may be clinically important in some cases. In this review we discuss implications for possible AQP4 disruption on NeuroHIV disease trajectory and how HIV may influence AQP4 function.

show abstract

Downregulation of A2AR by siRNA loaded PEG-chitosan-lactate nanoparticles restores the T cell mediated anti-tumor responses through blockage of PKA/CREB signaling pathway

Cited by 61 publications

References 39 publications

Blockage of immune checkpoint molecules increases T‐cell priming potential of dendritic cell vaccine

Blockage of immune checkpoint molecules increases T‐cell priming potential of dendritic cell vaccine

Immune checkpoint molecules in natural killer cells as potential targets for cancer immunotherapy

Astrocytes, HIV and the Glymphatic System: A Disease of Disrupted Waste Management?

Contact Info

Product

Resources

About