Scholars@Duke
Katayoun Ayasoufi

Katayoun Ayasoufi

Assistant Professor in Neurosurgery
Neurosurgery
katayoun.ayasoufi@duke.edu
303 Research Dr, Box 2600, Durham, NC 27710
303 Research Dr, MSRB 1-417, Durham, NC 27710

Selected Publications

Data from Anti-PD-1 and extended half-life-IL-2 synergize for treatment of murine glioblastoma independent of host MHC Class I expression

Other · September 16, 2024 <div>Abstract<p>Glioblastoma (GBM) is the most common malignant brain tumor in adults, responsible for approximately 225,000 deaths per year. Despite pre-clinical successes, most interventions have failed to extend patient survival by m ... Full text Cite

Microglial P2Y6 calcium signaling promotes phagocytosis and shapes neuroimmune responses in epileptogenesis.

Journal Article Neuron · June 19, 2024 Microglial calcium signaling is rare in a baseline state but strongly engaged during early epilepsy development. The mechanism(s) governing microglial calcium signaling are not known. By developing an in vivo uridine diphosphate (UDP) fluorescent sensor, G ... Full text Link to item Cite

TREM2 mediates MHCII-associated CD4+ T-cell response against gliomas.

Journal Article Neuro Oncol · May 3, 2024 BACKGROUND: Myeloid cells comprise up to 50% of the total tumor mass in glioblastoma (GBM) and have been implicated in promoting tumor progression and immunosuppression. Modulating the response of myeloid cells to the tumor has emerged as a promising new a ... Full text Link to item Cite

Discrete class I molecules on brain endothelium differentially regulate neuropathology in experimental cerebral malaria.

Journal Article Brain · February 1, 2024 Cerebral malaria is the deadliest complication that can arise from Plasmodium infection. CD8 T-cell engagement of brain vasculature is a putative mechanism of neuropathology in cerebral malaria. To define contributions of brain endothelial cell major histo ... Full text Link to item Cite

Brain resident memory T cells rapidly expand and initiate neuroinflammatory responses following CNS viral infection.

Journal Article Brain Behav Immun · August 2023 The contribution of circulating verses tissue resident memory T cells (TRMs) to clinical neuropathology is an enduring question due to a lack of mechanistic insights. The prevailing view is TRMs are protective against pathogens in the brain. However, the e ... Full text Link to item Cite

Chemogenetic manipulation of CX3CR1+ cells transiently induces hypolocomotion independent of microglia.

Journal Article Mol Psychiatry · July 2023 Chemogenetic approaches using Designer Receptors Exclusively Activated by Designer Drugs (DREADD, a family of engineered GPCRs) were recently employed in microglia. Here, we used Cx3cr1CreER/+:R26hM4Di/+ mice to express Gi-DREADD (hM4Di) on CX3CR1+ cells, ... Full text Link to item Cite

Anti-PD-1 and Extended Half-life IL2 Synergize for Treatment of Murine Glioblastoma Independent of Host MHC Class I Expression.

Journal Article Cancer Immunol Res · June 2, 2023 Glioblastoma (GBM) is the most common malignant brain tumor in adults, responsible for approximately 225,000 deaths per year. Despite preclinical successes, most interventions have failed to extend patient survival by more than a few months. Treatment with ... Full text Link to item Cite

Data from Anti–PD-1 and Extended Half-life IL2 Synergize for Treatment of Murine Glioblastoma Independent of Host MHC Class I Expression

Other · June 2, 2023 <div>Abstract<p>Glioblastoma (GBM) is the most common malignant brain tumor in adults, responsible for approximately 225,000 deaths per year. Despite preclinical successes, most interventions have failed to extend patient survival by mo ... Full text Cite

Data from Anti–PD-1 and Extended Half-life IL2 Synergize for Treatment of Murine Glioblastoma Independent of Host MHC Class I Expression

Other · April 27, 2023 <div>Abstract<p>Glioblastoma (GBM) is the most common malignant brain tumor in adults, responsible for approximately 225,000 deaths per year. Despite preclinical successes, most interventions have failed to extend patient survival by mo ... Full text Cite

Systemic immune derangements are shared across various CNS pathologies and reflect novel mechanisms of immune privilege.

Journal Article Neurooncol Adv · 2023 BACKGROUND: The nervous and immune systems interact in a reciprocal manner, both under physiologic and pathologic conditions. Literature spanning various CNS pathologies including brain tumors, stroke, traumatic brain injury and de-myelinating diseases des ... Full text Link to item Cite

AN OPTIMIZED MOUSE PARABIOSIS PROTOCOL FOR INVESTIGATION OF AGING AND REJUVENATIVE MECHANISMS

Journal Article Innovation in Aging · December 20, 2022 AbstractSurgical parabiosis is widely used to study the mechanistic influence of the circulating milieu on aging and regeneration. This powerful model presents diverse complications based on age, strain, sex ... Full text Cite

Rejuvenation of the aged brain immune cell landscape in mice through p16-positive senescent cell clearance.

Journal Article Nat Commun · September 27, 2022 Cellular senescence is a plausible mediator of inflammation-related tissue dysfunction. In the aged brain, senescent cell identities and the mechanisms by which they exert adverse influence are unclear. Here we used high-dimensional molecular profiling, co ... Full text Link to item Cite

An optimized mouse parabiosis protocol for investigation of aging and rejuvenative mechanisms

Journal Article Frontiers in Aging · January 1, 2022 Surgical parabiosis enables sharing of the circulating milieu between two organisms. This powerful model presents diverse complications based on age, strain, sex, and other experimental parameters. Here, we provide an optimized parabiosis protocol for the ... Full text Cite

Immune signatures underlying post-acute COVID-19 lung sequelae.

Journal Article Sci Immunol · November 12, 2021 Severe coronavirus disease 2019 (COVID-19) pneumonia survivors often exhibit long-term pulmonary sequelae, but the underlying mechanisms or associated local and systemic immune correlates are not known. Here, we have performed high-dimensional characteriza ... Full text Link to item Cite

Immunosuppression in Glioblastoma: Current Understanding and Therapeutic Implications

Journal Article Frontiers in Oncology · October 28, 2021 Glioblastoma (GBM) is the most common primary brain tumor in adults an carries and carries a terrible prognosis. The current regiment of surgical resection, radiation, and chemotherapy has remained largely unchanged in recent years as new therapeutic appro ... Full text Cite

Immunostimulatory bacterial antigen-armed oncolytic measles virotherapy significantly increases the potency of anti-PD1 checkpoint therapy.

Journal Article J Clin Invest · July 1, 2021 Clinical immunotherapy approaches are lacking efficacy in the treatment of glioblastoma (GBM). In this study, we sought to reverse local and systemic GBM-induced immunosuppression using the Helicobacter pylori neutrophil-activating protein (NAP), a potent ... Full text Link to item Cite

Microglia and Perivascular Macrophages Act as Antigen Presenting Cells to Promote CD8 T Cell Infiltration of the Brain.

Journal Article Front Immunol · 2021 CD8 T cell infiltration of the central nervous system (CNS) is necessary for host protection but contributes to neuropathology. Antigen presenting cells (APCs) situated at CNS borders are thought to mediate T cell entry into the parenchyma during neuroinfl ... Full text Link to item Cite

Anti-PD-1 checkpoint blockade monotherapy in the orthotopic GL261 glioma model: The devil is in the detail

Journal Article Neuro-Oncology Advances · January 1, 2021 The GL261 cell line, syngeneic on the C57BL/6 background, has, since its establishment half a century ago in 1970, become the most commonly used immunocompetent murine model of glioblastoma. As immunotherapy has entered the mainstream of clinical discourse ... Full text Cite

Brain cancer induces systemic immunosuppression through release of non-steroid soluble mediators.

Journal Article Brain · December 1, 2020 Immunosuppression of unknown aetiology is a hallmark feature of glioblastoma and is characterized by decreased CD4 T-cell counts and downregulation of major histocompatibility complex class II expression on peripheral blood monocytes in patients. This immu ... Full text Link to item Cite

Tissue-resident CD8+ T cells drive age-associated chronic lung sequelae after viral pneumonia.

Journal Article Sci Immunol · November 6, 2020 Lower respiratory viral infections, such as influenza virus and severe acute respiratory syndrome coronavirus 2 infections, often cause severe viral pneumonia in aged individuals. Here, we report that influenza viral pneumonia leads to chronic nonresolving ... Full text Link to item Cite

Conditional Silencing of H-2Db Class I Molecule Expression Modulates the Protective and Pathogenic Kinetics of Virus-Antigen-Specific CD8 T Cell Responses during Theiler's Virus Infection.

Journal Article J Immunol · September 1, 2020 Theiler's murine encephalomyelitis virus (TMEV) infection of the CNS is cleared in C57BL/6 mice by a CD8 T cell response restricted by the MHC class I molecule H-2Db The identity and function of the APC(s) involved in the priming of this T cell response is ... Full text Link to item Cite

Oncolytic virus-derived type I interferon restricts CAR T cell therapy.

Journal Article Nat Commun · June 24, 2020 The application of adoptive T cell therapies, including those using chimeric antigen receptor (CAR)-modified T cells, to solid tumors requires combinatorial strategies to overcome immune suppression associated with the tumor microenvironment. Here we test ... Full text Link to item Cite

Seek and hide: the manipulating interplay of measles virus with the innate immune system.

Journal Article Curr Opin Virol · April 2020 The innate immune system is the first line of defense against infections with pathogens. It provides direct antiviral mechanisms to suppress the viral life cycle at multiple steps. Innate immune cells are specialized to recognize pathogen infections and ac ... Full text Link to item Cite

Comparison of Gene Delivery to the Kidney by Adenovirus, Adeno-Associated Virus, and Lentiviral Vectors After Intravenous and Direct Kidney Injections.

Journal Article Hum Gene Ther · December 2019 There are many kidney diseases that might be addressed by gene therapy. However, gene delivery to kidney cells is inefficient. This is due, in part, to the fact that the kidney excludes molecules above 50 kDa and that most gene delivery vectors are megaDal ... Full text Link to item Cite

SCIDOT-34. BRAIN INJURY SIGNALS SYSTEMIC IMMUNOSUPPRESSION THROUGH THYMIC INVOLUTION

Journal Article Neuro-Oncology · November 11, 2019 AbstractSystemic immunosuppression following neurological insults including stroke, traumatic brain injury, and glioblastoma (GBM) causes mortality and leads to failure of immune-modulating therapies. Exact ... Full text Cite

Interleukin-27 promotes CD8+ T cell reconstitution following antibody-mediated lymphoablation.

Journal Article JCI Insight · April 4, 2019 Antibody-mediated lymphoablation is used in solid organ and stem cell transplantation and autoimmunity. Using murine anti-thymocyte globulin (mATG) in a mouse model of heart transplantation, we previously reported that the homeostatic recovery of CD8+ T ce ... Full text Link to item Cite

GM-CSF inhibition reduces cytokine release syndrome and neuroinflammation but enhances CAR-T cell function in xenografts.

Journal Article Blood · February 14, 2019 Chimeric antigen receptor T (CAR-T) cell therapy is a new pillar in cancer therapeutics; however, its application is limited by the associated toxicities. These include cytokine release syndrome (CRS) and neurotoxicity. Although the IL-6R antagonist tocili ... Full text Link to item Cite

GM-CSF Blockade during Chimeric Antigen Receptor T Cell Therapy Reduces Cytokine Release Syndrome and Neurotoxicity and May Enhance Their Effector Functions

Conference Blood · November 29, 2018 AbstractDespite its efficacy, chimeric antigen receptor T-cell therapy (CART) is limited by the development of cytokine release syndrome (CRS) and neurotoxicity (NT). While CRS is r ... Full text Cite

Aquaporin 4 blockade improves survival of murine heart allografts subjected to prolonged cold ischemia.

Journal Article Am J Transplant · May 2018 Prolonged cold ischemia storage (CIS) is a leading risk factor for poor transplant outcome. Existing strategies strive to minimize ischemia-reperfusion injury in transplanted organs, yet there is a need for novel approaches to improve outcomes of marginal ... Full text Link to item Cite

Allograft dendritic cell p40 homodimers activate donor-reactive memory CD8+ T cells.

Journal Article JCI Insight · February 22, 2018 Recipient endogenous memory T cells with donor reactivity pose an important barrier to successful transplantation and costimulatory blockade-induced graft tolerance. Longer ischemic storage times prior to organ transplantation increase early posttransplant ... Full text Link to item Cite

Immunomodulation Mediated by Anti-angiogenic Therapy Improves CD8 T Cell Immunity Against Experimental Glioma.

Journal Article Front Oncol · 2018 Glioblastoma (GBM) is a lethal cancer of the central nervous system with a median survival rate of 15 months with treatment. Thus, there is a critical need to develop novel therapies for GBM. Immunotherapy is emerging as a promising therapeutic strategy. H ... Full text Link to item Cite

Growth Associated Protein 43 (GAP-43) as a Novel Target for the Diagnosis, Treatment and Prevention of Epileptogenesis.

Journal Article Sci Rep · December 18, 2017 We previously showed increased growth associated protein 43 (GAP-43) expression in brain samples resected from patients with cortical dysplasia (CD), which was correlated with duration of epilepsy. Here, we used a rat model of CD to examine the regulation ... Full text Link to item Cite

Depletion-Resistant CD4 T Cells Enhance Thymopoiesis During Lymphopenia.

Journal Article Am J Transplant · August 2017 Lymphoablation is routinely used in transplantation, and its success is defined by the balance of pathogenic versus protective T cells within reconstituted repertoire. While homeostatic proliferation and thymopoiesis may both cause T cell recovery during l ... Full text Link to item Cite

Role of Memory T Cells in Allograft Rejection and Tolerance.

Journal Article Front Immunol · 2017 Memory T cells are characterized by their low activation threshold, robust effector functions, and resistance to conventional immunosuppression and costimulation blockade. Unlike their naïve counterparts, memory T cells reside in and recirculate through pe ... Full text Link to item Cite

CD4 T Cell Help via B Cells Is Required for Lymphopenia-Induced CD8 T Cell Proliferation.

Journal Article J Immunol · April 1, 2016 Ab-mediated lymphoablation is commonly used in solid organ and hematopoietic cell transplantation. However, these strategies fail to control pathogenic memory T cells efficiently and to improve long-term transplant outcomes significantly. Understanding the ... Full text Link to item Cite

Platelet hyaluronidase-2: an enzyme that translocates to the surface upon activation to function in extracellular matrix degradation.

Journal Article Blood · February 26, 2015 Following injury, platelets rapidly interact with the exposed extracellular matrix (ECM) of the vessel wall and the surrounding tissues. Hyaluronan (HA) is a major glycosaminoglycan component of the ECM and plays a significant role in regulating inflammati ... Full text Link to item Cite

B cell activating factor (BAFF) and a proliferation inducing ligand (APRIL) mediate CD40-independent help by memory CD4 T cells.

Journal Article Am J Transplant · February 2015 Donor-reactive memory T cells undermine organ transplant survival and are poorly controlled by immunosuppression or costimulatory blockade. Memory CD4 T cells provide CD40-independent help for the generation of donor-reactive effector CD8 T cells and alloa ... Full text Link to item Cite

Pretransplant antithymocyte globulin has increased efficacy in controlling donor-reactive memory T cells in mice.

Journal Article Am J Transplant · March 2013 Antibody-mediated lymphocyte depletion is frequently used as induction therapy in sensitized transplant patients. Although T cells with an effector/memory phenotype remain detectable after lymphoablative therapies in human transplant recipients, the role o ... Full text Link to item Cite

Pre-transplant administration of antithymocyte globulin increases its efficacy in inhibiting anti-donor memory T cell responses (126.9)

Journal Article The Journal of Immunology · May 1, 2012 AbstractAntithymocyte globulin (ATG) is a lymphoablative agent used in transplant patients. In this study, we tested how murine analog of ATG (mATG)affects pre-existent donor-reactive memory T cells. mATG tr ... Full text Cite

Upright imaging of Drosophila embryos.

Journal Article J Vis Exp · September 13, 2010 Several well-known morphogenetic gradients and cellular movements occur along the dorsal/ventral axis of the Drosophila embryo. However, the current techniques used to view such processes are somewhat limited. The following protocol describes a new techniq ... Full text Link to item Cite