Kelly Hotchkiss

ORCID: 0000-0001-9175-1579
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About
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Research Areas
  • Glioma Diagnosis and Treatment
  • Immunotherapy and Immune Responses
  • CAR-T cell therapy research
  • Cancer Immunotherapy and Biomarkers
  • Immune cells in cancer
  • Cancer Research and Treatments
  • Bone Tissue Engineering Materials
  • Orthopaedic implants and arthroplasty
  • Cancer, Stress, Anesthesia, and Immune Response
  • Graphene and Nanomaterials Applications
  • RNA Interference and Gene Delivery
  • Nanoplatforms for cancer theranostics
  • Cancer Mechanisms and Therapy
  • Ferroptosis and cancer prognosis
  • Melanoma and MAPK Pathways
  • Neuroinflammation and Neurodegeneration Mechanisms
  • Bone Metabolism and Diseases
  • Receptor Mechanisms and Signaling
  • vaccines and immunoinformatics approaches
  • Titanium Alloys Microstructure and Properties
  • Cancer Treatment and Pharmacology
  • Chemokine receptors and signaling
  • Endodontics and Root Canal Treatments
  • Nanoparticles: synthesis and applications
  • Wnt/β-catenin signaling in development and cancer

Duke University
2020-2025

Duke University Hospital
2021-2024

Virginia Commonwealth University
2014-2024

Duke Medical Center
2020-2024

Abstract Objectives To determine the effects of dental implant surface chemistry and energy on macrophage activation in vitro . Materials Methods Disks made from two clinically used materials (titanium [Ti], titanium zirconium alloy [TiZr]) were produced with different treatments (sandblast/acid‐etch [ SLA ], hydrophilic‐ [mod ]). Surface roughness, energy, characterized. Primary murine macrophages isolated 6‐ to 8‐week‐old male C57Bl/6 mice cultured test surfaces (Ti , TiZr Ti mod ) or...

10.1111/clr.12814 article EN Clinical Oral Implants Research 2016-03-23

Titanium (Ti) and Ti alloys are used in orthopaedic/spine applications where biological implant fixation, or osseointegration, is required for long-term stability. These implants employ macro-scale features to provide mechanical stability until arthrodesis, that too large influence healing at the cellular level. Micron-scale rough alloy (Ti–6Al–4V) increases osteoblastic differentiation osteogenic factor production vitro vivo bone formation; however, effects of overall topography, including...

10.1007/s10439-014-1108-3 article EN cc-by Annals of Biomedical Engineering 2014-09-17

Roughened dental implants promote mesenchymal stem cell (MSCs) osteoblastic differentiation, and hydrophilic modifications induce anti-inflammatory macrophages activation. While the effect of different surface on osseointegration commercial have been compared in vivo clinically, initial cellular response to these often overlooked. We aimed characterize macrophage inflammatory MSC osteogenesis across commercially available vitro.Six rough [OsseoSpeed™ (Astra-Tech™, Implant A); Osseotite®...

10.1016/j.dental.2018.11.011 article EN cc-by-nc-nd Dental Materials 2018-11-30

<title>Abstract</title> Many cancers evade immunosurveillance by downregulating surface major histocompatibility class (MHC)-I. Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes MHC-I degradation and is elevated in glioma. Evolocumab a clinically approved PCSK9 inhibitor, which restores expression pre-clinical cancer models. However, monoclonal antibodies (mAbs) have limited blood brain/tumor barrier penetrance (BBB/BTB). The aim of this window-of-opportunity trial was to...

10.21203/rs.3.rs-5822396/v1 preprint EN cc-by Research Square (Research Square) 2025-01-22

Tumor-infiltrating lymphocyte (TIL) therapy, recently approved by the FDA for melanoma, is an emerging modality cell-based immunotherapy. However, its application in immunologically 'cold' tumors such as glioblastoma remains limited due to sparse T cell infiltration, antigenic heterogeneity, and a suppressive tumor microenvironment. To identify genomic spatial determinants of TIL expandability, we performed integrated, multimodal profiling high-grade gliomas using spectral flow cytometry,...

10.1101/2025.03.26.645566 preprint EN cc-by-nc-nd bioRxiv (Cold Spring Harbor Laboratory) 2025-03-31

The efficacy of T cell-activating therapies against glioma is limited by an immunosuppressive tumor microenvironment and tumor-induced cell sequestration. We investigated whether peripherally infused non-antigen specific autologous lymphocytes (ALT) could accumulate in intracranial tumors. observed that non-specific CD8+ ALT cells can indeed this context, despite endogenous sequestration bone marrow. Rates intratumoral accumulation were markedly increased when expanding with IL-7 compared to...

10.1172/jci181471 article EN cc-by Journal of Clinical Investigation 2025-04-17

Abstract Introduction: EGFRvIII is a commonly studied tumor-specific antigen in glioblastoma (GBM) and poses an enticing target for immunotherapy. Its varied expression, however, complicates its effectiveness as Chimeric Antigen Receptor (CAR) T cell target. Given the increasing prominence of Interleukin-12 (IL12) treating solid tumors, synergy with specific CARs preclinical models GBM explored. Methods: To simulate tumor heterogeneity, mice were implanted equal ratios CT2A EGFRvIII+ cells....

10.1158/1538-7445.am2024-4006 article EN Cancer Research 2024-03-22

The efficacy of T cell-dependent immunotherapies against glioma is limited by few intra-tumoral lymphocytes and tumor-induced cell sequestration. We considered whether peripheral autologous lymphocyte transfer (ALT) could boost Central Nervous System (CNS) counts in established glioma. found that ALT specifically entered tumor tissue while endogenous fell. cells expanded with IL-7 demonstrated an enhanced ability to accumulate murine compared IL-2. Increased entry was not phenotype...

10.1101/2024.04.01.587634 preprint EN cc-by-nc-nd bioRxiv (Cold Spring Harbor Laboratory) 2024-04-01

Abstract Many cancers, including glioma, evade immunosurveillance by downregulating surface major histocompatibility class (MHC)-I. Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes degradation of multiple receptors, MHC-I and peripheral levels are specifically elevated in glioma (Human Protein Atlas). Inhibition PCSK9 (PCSK9i) blocks degradation. Evolocumab is a PCSK9i monoclonal antibody (mAb) indicated for hyperlipidemia. However, mAbs have limited penetrance across the blood...

10.1101/2024.06.19.24309192 preprint EN cc-by-nc-nd medRxiv (Cold Spring Harbor Laboratory) 2024-06-20

Abstract Exhaustion represents a collection of programmed T cell differentiation states and an important mode dysfunction. progression from progenitor to terminal exhaustion is associated with upregulation the transcription factor TOX expression TIM3. Our understanding factors regulating transition exhaustion, however, remains incomplete. We reveal here that tumor necrosis receptor type II (TNFR2) coincides gain phenotypic markers functions reflective exhaustion. Meanwhile, knocking out...

10.1101/2024.07.12.603311 preprint EN bioRxiv (Cold Spring Harbor Laboratory) 2024-07-17

Abstract Checkpoint inhibitors have been very successful in various tumors, including melanoma and lung cancer. However, these treatments failed other pancreatic cancer glioblastoma. Approaches harnessing the immune response are hindered by multiple factors, T cell exhaustion. Exhausted cells less capable of limiting tumor progression. TOX is particularly important for transcriptional epigenetic reprogramming exhausted cells, without TOX, cannot differentiate down exhaustion pathway. While...

10.1158/2326-6074.tumimm24-a056 article EN Cancer Immunology Research 2024-10-18

Abstract Glioblastoma (GBM) is the most common primary brain cancer in adults with a median survival less than 15 months. Approaches harnessing immune response are hindered by multiple factors, including T cell exhaustion. Exhausted cells capable of limiting tumor progression. As progress along exhaustion pathway, SLAM Family Member 6 (SLAMF6) gets downregulated and immunoglobulin mucin domain-containing protein 3 (TIM3) TOX upregulated. both necessary sufficient to initiate terminal...

10.4049/jimmunol.212.supp.1490.5509 article EN The Journal of Immunology 2024-05-01
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