Sinonasal T-Cell Expression of Cytotoxic Mediators Granzyme B and Perforin is Reduced in Patients with Chronic Rhinosinusitis

Smith, Sarah E.; Schlosser, Rodney J.; Yawn, James; Mattos, José L.; Soler, Zachary M.; Mulligan, Jennifer K.

doi:10.2500/ajra.2017.31.4474

Cited by 5 publications

(8 citation statements)

References 37 publications

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“…In principle, GrB could also be delivered through this pathway. The CTLs release perforin and form pores on the surface of the target cell membrane, allowing direct diffusion of GrB into the cytoplasm of the cell thus helping its escape from endosome and lysosome degradation (Scheme 1a) 29-30. Consequently, abundant apoptosis pathways are activated, including caspase and BH3 interacting domain death (BID) agonist, and induce cell death (Scheme 1).…”

Section: Introductionmentioning

confidence: 99%

A novel Granzyme B nanoparticle delivery system simulates immune cell functions for suppression of solid tumors

Xiao-min¹,

Shi²,

Qi³

et al. 2019

Theranostics

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Cell-based immunotherapy for the treatment of hematologic malignancies, such as leukemia and lymphoma, has seen much success and played an increasingly important role in clinical studies. Nevertheless, the efficacy of immunotherapy in solid tumors still needs improvements due to the immunosuppressive properties of tumor cells and the microenvironment. To overcome these limitations, we prepared a novel tumor-targeting delivery system based on the underlying mechanism of immune-targeted cell death that encapsulated granzyme B protein within a porous polymeric nanocapsule.Methods: A cell-penetrating peptide TAT was attached onto granzyme B (GrB) to enhance its transmembrane transport efficiency and potency to induce cell apoptosis. The endocytosis and internalization pathways of GrB-TAT (GrB-T) were analyzed in comparison with perforin by confocal microscopy and flow cytometry. Furthermore, the positively charged GrB-T was wrapped into nanoparticles by p-2-methacryloyloxy ethyl phosphorylcholine (PMPC)-modified HA (hyaluronic acid). The nanoparticles (called TCiGNPs) were characterized in terms of zeta potential and by transmission electron microscopy (TEM). The in vitro anti-tumor effects of GrB-T were examined by cell apoptosis assay and Western blotting analysis. The in vivo anti-tumor therapeutic efficacy of TCiGNPs was evaluated in a mouse tumor model.Results: The TAT peptide could play a role similar to perforin to mediate direct transmembrane transfer of GrB and improve GrB-induced cell apoptosis. The TCiGNPs were successfully synthesized and accumulated in the solid tumor through enhanced permeability and retention (EPR) effect. In the tumor microenvironment, TCiGNPs could be degraded by hyaluronidase and triggered the release of GrB-T. The TAT peptide enabled the translocation of GrB across the plasma membrane to induce tumor cell apoptosis in vivo.Conclusion: We successfully developed a granzyme B delivery system with a GrB-T core and a PMPC/HA shell that simulated CTL/NK cell-mediated cancer immunotherapy mechanism. The GrB delivery system holds great promise for cancer treatment analogous to the CTL/NK cell-induced immunotherapy.

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Section: Introductionmentioning

confidence: 99%

A novel Granzyme B nanoparticle delivery system simulates immune cell functions for suppression of solid tumors

Xiao-min¹,

Shi²,

Qi³

et al. 2019

Theranostics

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“…Defective cytotoxic T-cell function has similarly also been implicated in the dysregulated immune response seen in CRS. 3 A novel study by Smith et al , 4 also published in this issue, set out to explore the mechanism behind this. In their study of patients with CRS with and without polyps, the investigators observed a decrease in the local production of the important cytotoxic T-cell mediators, granzyme B, and perforin, despite an increase in absolute cytotoxic T-cell numbers in the tissue of patients with CRS.…”

mentioning

confidence: 99%

“…In their study of patients with CRS with and without polyps, the investigators observed a decrease in the local production of the important cytotoxic T-cell mediators, granzyme B, and perforin, despite an increase in absolute cytotoxic T-cell numbers in the tissue of patients with CRS. 4 They postulated that it is possible that this deficiency may affect antiviral immunity and predispose patients with CRS to an exaggerated inflammatory response after a viral insult. 4…”

mentioning

confidence: 99%

“…4 They postulated that it is possible that this deficiency may affect antiviral immunity and predispose patients with CRS to an exaggerated inflammatory response after a viral insult. 4…”

mentioning

confidence: 99%

“…4 They postulated that it is possible that this deficiency may affect antiviral immunity and predispose patients with CRS to an exaggerated inflammatory response after a viral insult. 4 Understanding the pathophysiology of CRS may also afford better diagnostic and monitoring techniques, and allow for new treatment development. Liu et al 5 reported their findings on the possible use of exhaled nitric oxide as a noninvasive biomarker for classifying polyp status in patients with CRS.…”

mentioning

confidence: 99%

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Beyond Borders and Sinuses: Rhinology and Allergy Research on a World Stage

Psaltis¹

2017

Am J Rhinol�Allergy

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Beyond borders and sinuses: Rhinology and allergy research on a world stage R esearch forms the keystone on which medicine is advanced. It improves our understanding of the disease process and paves the way for new treatment development. This journal prides itself on the publishing of well-performed basic science and clinical research. Its adherence to a rigorous peer-review process and the careful selection of diverse articles maintains its high quality and its relevance to the broad readership. This issue, in particular, exemplifies the international presence of American Journal of Rhinology & Allergy (AJRA), with as many articles from abroad as from local research groups. Basic science, translational, and clinical research articles from the United States, Europe, Asia, and the Middle East comprise this installment of the AJRA, with diverse topics to interest both clinicians and scientists. Novel biomarkers for predicting polyps status, topical therapy to improve nasal continuous positive airway pressure (CPAP) compliance, and the use of gels and/or stents to improve surgical outcomes are among the many interesting articles available to the reader.Inflammatory upper airway disorders remain among the most common chronic conditions that confront primary health care providers and otolaryngologists. Most recent estimates indicate that the overall cost of chronic rhinosinusitis (CRS) to the American population exceeds 20 billion dollars per year. 1 Although patients often look to surgery as a "cure" for their condition, most clinicians would agree that the main role of surgery is to reduce the inflammatory burden and improve the access of the sinuses to topical medications. It is not until the complex inflammatory pathways are completely discerned that a "cure" will ever be achievable. An important step forward toward this requires an understanding of the pathophysiology at an immunologic level. The relatively recent discovery of the regulatory T cells and their role in CRS was a significant breakthrough. These cells seem to play a central immunomodulatory role in inflammatory nasal disease and may hold the key to controlling the dysregulated inflammation seen in these conditions.In this issue of the AJRA, Palmer et al., 2 provided a comprehensive review of the role of regulatory T cells in upper airways inflammation and identified current deficiencies in our understanding of their function. Defective cytotoxic T-cell function has similarly also been implicated in the dysregulated immune response seen in CRS. 3 A novel study by Smith et al., 4 also published in this issue, set out to explore the mechanism behind this. In their study of patients with CRS with and without polyps, the investigators observed a decrease in the local production of the important cytotoxic T-cell mediators, granzyme B, and perforin, despite an increase in absolute cytotoxic T-cell numbers in the tissue of patients with CRS. 4 They postulated that it is possible that this deficiency may affect antiviral immunity and predispose patients with ...

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Digital diaphanoscopy of maxillary sinus pathologies supported by machine learning

Bryanskaya

Dremin

Shupletsov

et al. 2023

Journal of Biophotonics

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Maxillary sinus pathologies remain among the most common ENT diseases requiring timely diagnosis for successful treatment. Standard ENT inspection approaches indicate low sensitivity in detecting maxillary sinus pathologies. In this paper, we report on capabilities of digital diaphanoscopy combined with machine learning tools in the detection of such pathologies. We provide a comparative analysis of two machine learning approaches applied to digital diapahnoscopy data, namely, convolutional neural networks and linear discriminant analysis. The sensitivity and specificity values obtained for both employed approaches exceed the reported accuracy indicators for traditional screening diagnosis methods (such as nasal endoscopy or ultrasound), suggesting the prospects of their usage for screening maxillary sinuses alterations. The analysis of the obtained values showed that the linear discriminant analysis, being a simpler approach as compared to neural networks, allows one to detect the maxillary sinus pathologies with the sensitivity and specificity of 0.88 and 0.98, respectively.

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Sinonasal T-Cell Expression of Cytotoxic Mediators Granzyme B and Perforin is Reduced in Patients with Chronic Rhinosinusitis

Abstract: ABSTRACT

Cited by 5 publications

References 37 publications

A novel Granzyme B nanoparticle delivery system simulates immune cell functions for suppression of solid tumors

A novel Granzyme B nanoparticle delivery system simulates immune cell functions for suppression of solid tumors

Beyond Borders and Sinuses: Rhinology and Allergy Research on a World Stage

Digital diaphanoscopy of maxillary sinus pathologies supported by machine learning

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