Browsing by Author "Cohen‑Gadol, Aaron A."

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    Functional expression of CD73 on human natural killer cells
    (Springer, 2022) Chambers, Andrea M.; Wang, Jiao; Dao, Tram N.; Lupo, Kyle B.; Veenhuis, Paige; Ayers, Mitchell G.; Slivova, Veronika; Cohen‑Gadol, Aaron A.; Matosevic, Sandro; Neurological Surgery, School of Medicine
    The production of adenosine by CD73 on cancer cells in the tumor microenvironment is a recognized immunosuppressive mechanism contributing to immune evasion in many solid tumors. While NK cells have been purported to overexpress CD73 under certain conditions, this phenomenon has remained elusive and unclear. We have found that while NK cells are able to upregulate expression of CD73 on their surface when exposed to CD73+ cancer cells, this upregulation is not universal, nor is it often substantial. Rather, our data point to the extent of CD73 expression on NK cells to be both cancer-specific and environmentally-driven, and largely limited in intensity. We found that NK cell overexpression of CD73 responds to the level of CD73 on cancer cells and is enhanced in hypoxia. Interestingly, human CD73+ NK cells appear hyperfunctional in vitro compared to CD73- NK cells, suggesting that CD73 expression could be a bystander of NK cell activation. In addition, glioblastoma patient data show that tumor-infiltrating NK cells express CD73 variably, depending on donor, and present lower expression of CD16, alongside patient-specific changes in CEACAM1, CXCR3 and TIM-3, suggesting some functional changes in NK cell responses associated with expression of CD73 on NK cells in vivo. Taken together, our study is the first to show that while NK cells are largely resistant to the upregulation of CD73, CD73 expression is inducible on NK cells in response to CD73 on cancer cells, and these cells are associated with distinct functional signatures.
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    Functional expression of CD73 on human natural killer cells
    (Springer, 2022) Chambers, Andrea M.; Wang, Jiao; Dao, Tram N.; Lupo, Kyle B.; Veenhuis, Paige; Ayers, Mitchell G.; Slivova, Veronika; Cohen‑Gadol, Aaron A.; Matosevic, Sandro; Neurological Surgery, School of Medicine
    The production of adenosine by CD73 on cancer cells in the tumor microenvironment is a recognized immunosuppressive mechanism contributing to immune evasion in many solid tumors. While NK cells have been purported to overexpress CD73 under certain conditions, this phenomenon has remained elusive and unclear. We have found that while NK cells are able to upregulate expression of CD73 on their surface when exposed to CD73+ cancer cells, this upregulation is not universal, nor is it often substantial. Rather, our data point to the extent of CD73 expression on NK cells to be both cancer-specific and environmentally-driven, and largely limited in intensity. We found that NK cell overexpression of CD73 responds to the level of CD73 on cancer cells and is enhanced in hypoxia. Interestingly, human CD73+ NK cells appear hyperfunctional in vitro compared to CD73− NK cells, suggesting that CD73 expression could be a bystander of NK cell activation. In addition, glioblastoma patient data show that tumor-infiltrating NK cells express CD73 variably, depending on donor, and present lower expression of CD16, alongside patient-specific changes in CEACAM1, CXCR3 and TIM-3, suggesting some functional changes in NK cell responses associated with expression of CD73 on NK cells in vivo. Taken together, our study is the first to show that while NK cells are largely resistant to the upregulation of CD73, CD73 expression is inducible on NK cells in response to CD73 on cancer cells, and these cells are associated with distinct functional signatures.
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    The extended supracerebellar transtentorial approach for resection of medial tentorial meningiomas
    (Scientific Scholar, 2014-03-15) Ansari, Shaheryar F.; Young, Ronald L.; Bohnstedt, Bradley N.; Cohen‑Gadol, Aaron A.; Neurological Surgery, School of Medicine
    Background: The supracerebellar transtentorial (SCTT) approach has been established as a safe corridor to access the posteriomedial basal temporal region. Previous reports have demonstrated the efficacy of this route in the resection of intrinsic tumors and small arteriovenous malformations. Only one report in the English literature has described its use to resect a medial tentorial meningioma. Methods: The authors discuss the relevant surgical anatomy of this approach and its advantages compared with more traditional routes, and illustrate its application to remove medial tentorial meningiomas through two operative cases with accompanying videos. Results: In illustrative case one, the patient recovered from surgery with no deficits. All his preoperative symptoms had resolved at 3-month follow-up. At the 4-year follow-up, MRI did not demonstrate any growth of the residual tumor. In case two, gross total resection was achieved and the patient did not suffer any postoperative language or visual deficit. At 2-year follow-up, no tumor recurrence was present. Conclusion: The SCTT approach has a potential to safely access extra-axial lesions located around the medial tentorial incisura. As demonstrated in these two cases, the approach merits consideration in patients with tentorial meningiomas as an alternative to more widely utilized skull base approaches and subtemporal routes.