Browsing by Author "Kwon, Jae Hyun"

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    Aging- and Tumor-Mediated Increase in CD8+CD28- T Cells Might Impose a Strong Barrier to Success of Immunotherapy in Glioblastoma
    (American Association of Immunologists, 2021-06-08) Huff, Wei X.; Bam, Marpe; Shireman, Jack M.; Kwon, Jae Hyun; Song, Leo; Newman, Sharlé; Cohen-Gadol, Aaron A.; Shapiro, Scott; Jones, Tamara; Fulton, Kelsey; Liu, Sheng; Tanaka, Hiromi; Liu, Yunlong; Wan, Jun; Dey, Mahua; Neurological Surgery, School of Medicine
    Clinical use of various forms of immunotherapeutic drugs in glioblastoma (GBM), has highlighted severe T-cell dysfunction such as exhaustion in GBM patients. However, reversing T-cell exhaustion using immune checkpoint inhibitors in GBM clinical trials has not shown significant overall survival benefit. Phenotypically, CD8+ T cells with downregulated CD28 co-receptors, low CD27 expression, increased CD57 expression, and telomere shortening, are classified as senescent T cells. These senescent T cells are normally seen as part of aging and also in many forms of solid cancers. Absence of CD28 on T-cells leads to several functional irregularities including reduced TCR diversity, incomplete activation of T cells, and defects in antigen induced proliferation. In the context of GBM, presence and/or function of these CD8+CD28− T-cells is unknown. In this clinical correlative study, we investigated the effect of aging as well as tumor microenvironment on CD8+ T-cell phenotype as an indicator of its function in GBM patients. We systematically analyzed and describe a large population of CD8+CD28− T-cells in both the blood and tumor infiltrating lymphocytes of GBM patients. We found that phenotypically these CD8+CD28− T-cells represent a distinct population compared to exhausted T-cells. Comparative transcriptomic and pathway analysis of CD8+CD28− T cell populations in GBM patients revealed that tumor microenvironment might be influencing several immune related pathways and thus further exaggerating the age associated immune dysfunction in this patient population.
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    The Evolving Role of CD8+CD28- Immunosenescent T Cells in Cancer Immunology
    (MDPI, 2019-06-08) Huff, Wei X.; Kwon, Jae Hyun; Henriquez, Mario; Fetcko, Kaleigh; Dey, Mahua; Neurosurgery, IU School of Medicine
    Functional, tumor-specific CD8+ cytotoxic T lymphocytes drive the adaptive immune response to cancer. Thus, induction of their activity is the ultimate aim of all immunotherapies. Success of anti-tumor immunotherapy is precluded by marked immunosuppression in the tumor microenvironment (TME) leading to CD8+ effector T cell dysfunction. Among the many facets of CD8+ T cell dysfunction that have been recognized-tolerance, anergy, exhaustion, and senescence-CD8+ T cell senescence is incompletely understood. Naïve CD8+ T cells require three essential signals for activation, differentiation, and survival through T-cell receptor, costimulatory receptors, and cytokine receptors. Downregulation of costimulatory molecule CD28 is a hallmark of senescent T cells and increased CD8+CD28- senescent populations with heterogeneous roles have been observed in multiple solid and hematogenous tumors. T cell senescence can be induced by several factors including aging, telomere damage, tumor-associated stress, and regulatory T (Treg) cells. Tumor-induced T cell senescence is yet another mechanism that enables tumor cell resistance to immunotherapy. In this paper, we provide a comprehensive overview of CD8+CD28- senescent T cell population, their origin, their function in immunology and pathologic conditions, including TME and their implication for immunotherapy. Further characterization and investigation into this subset of CD8+ T cells could improve the efficacy of future anti-tumor immunotherapy.
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    Management of Type III Occipital Condyle Fractures
    (MDPI, 2024-12-15) Kwon, Jae Hyun; Chinthala, Anoop Sai; Arnold, Jonathan C.; Witten, Andrew J.; Bohnstedt, Bradley N.; Neurological Surgery, School of Medicine
    Background/Objectives: Occipital condyle fractures (OCFs) can be seen in around 4-19% of patients who suffer from cervical spine trauma. Anderson and Montesano system type III OCFs, which are avulsion fractures, are potentially unstable and operative. This study evaluates the management of type III OCFs at our institution over a 22-year period. Methods: This retrospective study reviewed all cases of type III OCFs at our institution from July 2001 to March 2023, identified via imaging reports. Using the in-house radiology imaging informatics system "Doris" (Dig Our Radiology Information System), reports containing the terms subluxation, avulsion, unstable, or type 3/III with occipital condyle, occipital condylar, occipital fx, or occipital fracture were collected. We also searched for Montesano type III/3 fracture. Electronic medical records were used to collect clinical and demographic data. Patients evaluated by the neurosurgical team with at least 1 month of follow-up were included in the analysis. Results: A total of 563 patients were identified with type III OCFs. A total of 56 patients met the inclusion criteria. The majority (91%, 51/56) were treated conservatively with cervical orthosis. A small subset (8.9%, 5/56) underwent occipito-cervical fusion. Three had concomitant unstable C1 fractures, while the other two had significant coronal deformity associated with their type III OCF. Conclusions: At our institution, type III OCFs are predominantly managed with cervical orthosis. Only those with an associated malalignment of the occipito-cervical joint underwent fusion. These findings suggest that most type III OCFs can be treated conservatively with orthosis once stability is confirmed with an upright radiograph.