Justin Liu

All Publications

• Endogenous immune recruitment in glioblastoma CAR T therapy: cytokine, myeloid, and chemokine circuitry. Journal of neuro-oncology Liu, J., Abikenari, M., Annagiri, S., Ha, J. H., Nageeb, G., Sjoholm, M. A., Velazhahan, V., Medikonda, R., Choi, J., Li, G., Lim, M. 2026; 177 (1)

  Abstract

  Glioblastoma (GBM) has remained relatively unresponsive to immunotherapy, with scattered durable responses reported in early CAR T-cell studies, but without clear benefit at the population level. The major challenge for GBM has been its heterogeneous nature with a significantly immunosuppressive microenvironment that is predominantly composed of myeloid cells, inhibiting T-cell infiltration, function, and providing a rapid pathway for adaptive resistance. The focus of this review is to reposition GBM CAR T-cell therapy as a systems-level issue, turning localized CAR T-cell cytotoxicity into sustained control of the disease by engaging endogenous antitumor immunity via cytokine myeloid chemokine networks.We integrated both mechanism- and translation-oriented evidence for how inflammatory mediators derived from CAR T cells (Type I IFNs, IFN-γ, TNF) may license microglia/tumor-associated macrophages for antigen presentation and chemokine secretion, thus recruiting host effector cells and promoting antigen epitope spreading. To place this work within the context of current engineering trends, the current paper undertook a structured meta-synthesis on registry trials for interventional CAR T therapy for GBM using ClinicalTrials.gov. Using a structured advanced search strategy, we searched 91 registry records, found 44 trials for interventional CAR T therapy, and evaluated 23 active trials commenced after January 2020. Trials were classified based on target antigen choice, multi-antigen OR-gated approaches, conditional AND-gated synNotch logic, as well as safety and controllability measures (inducible off-switches).The effectiveness of CAR T cells for GBM is not likely to be actualized by targeting alone and needs to incorporate both killing and productive self-reinforcing endogenous immunity via myeloid licensing and chemokine amplification. Current trials are increasingly integrating this paradigm with a focus on more comprehensive antigens, gated CARs, immune-conjugate payloads, and safety designs amenable to the CNS without major toxicity such as ICANS. Future translation will require a focus on implementing endogenous immune activation as a quantified endpoint (including cytokine and chemokine analysis within CSF) and a simultaneous focus on immune set points that maintain cross-priming and memory without unmasking neuroinflammatory toxicity.

  View details for DOI 10.1007/s11060-026-05497-4

  View details for PubMedID 41820710

  View details for PubMedCentralID 11456825

• When Central Tolerance Fails: Thymic Malignancies at the Intersection of Cancer Immunity and Autoimmunity. Cancers Abikenari, M., Choi, J., Enayati, I., Tucker, A., Bhatnagar, K., Chen, Y., Himic, V., Liu, J., Nageeb, G., Poe, J., Ong, S. J., Sanker, V., Diehl, M., Szeifert, V., Terasaki, A., Prolo, L. M., Engleman, E., Okwan-Duodu, D. 2026; 18 (5)

  Abstract

  Thymic malignancies are rare cancers arising from thymic epithelial cells and are characterized by a highly diverse clinical phenotype, substantial histologic and morphologic heterogeneity, and frequent associations with autoimmune syndromes. Although the clinical, immunological, and cytoarchitectural changes associated with thymomas have been increasingly elucidated in the contemporary literature, very few studies have interrogated the direct role of tumor staging and histological grading in shaping autoimmunity burden and infection risk. In this narrative review, we synthesize contemporary clinical, immunological, and morphologic evidence linking thymic architecture and selection defects to the spectrum of paraneoplastic autoimmunity (MG, pure red cell aplasia, Good's syndrome) and to infectious vulnerability. We further appraise emerging therapeutic strategies, including immune checkpoint inhibition and adoptive cellular approaches, through a patient-stratified lens, emphasizing efficacy signals, immune-related adverse events, and practical considerations for selection and monitoring. We conclude by highlighting priorities for future investigation, including refining autoantibody signatures; mapping thymic microenvironments that drive tolerance failure, and prospectively evaluating stratified immunotherapeutic regimens that balance benefit with immune-mediated risk.

  View details for DOI 10.3390/cancers18050747

  View details for PubMedID 41827683

• Risk-stratified management of ankylosing spondylitis-related spinal fractures-a meta-synthesis of contemporary surgical and nonsurgical strategies: a narrative review. Journal of spine surgery (Hong Kong) Abikenari, M. A., Yoo, K. H., Liu, J., Ha, J., Nageeb, G., Jain, B., Park, L., Hani, U., Veeravagu, A. 2025; 11 (4): 1095-1110

  Abstract

  Ankylosing spondylitis (AS) spinal fractures pose unique diagnostic and therapeutic challenges due to the altered biomechanics, rigid ankylosed spine, and risk for extensive neurologic injury. The optimal practice is not established with rising clinical occurrences. This article aims to review the current literature regarding diagnosis, classification, and operative and non-operative treatment paradigms of spinal fractures due to AS in adults and present a cohesive perspective to facilitate evidence-based clinical practice.A narrative systematic review was conducted on the basis of the PubMed database, including English-language papers from January 2000 to May 2025. Keywords included "AS", "spinal fracture", "vertebral trauma", "surgical management", and "neurological outcomes". Studies identified were evaluated based on clinical relevance, level of evidence, and representation of evolving concepts in diagnosis and management.The review discusses the specific biomechanical frailties of the ankylosed spine, recent classification methods like AO Spine and Denis classifications, and recent imaging modalities for diagnosis. It highlights operative decision-making approaches, posterior-only, anterior, and combination, in fracture morphology, neurologic status, and patient comorbidities. It discusses perioperative concerns such as positioning issues, blood loss, and complications like hardware failure and infection. Four summary tables provide insight into imaging preference, surgical interventions, outcomes, and complication profiles.Prompt diagnosis and personalized treatment of AS-related spinal fractures are essential to reducing morbidity and mortality. Emerging literature supports the use of posterior-only methods in selected cases, but highly context-specific surgical choices must remain. The review stresses the importance of prospective studies as a guide to standard treatment protocols and improved outcomes for this difficult patient group.

  View details for DOI 10.21037/jss-25-119

  View details for PubMedID 41509825

  View details for PubMedCentralID PMC12775638

• Adaptive immunotherapeutic paradigms in diffuse midline glioma: integrating epigenetic reprogramming, neuron-glioma interactions, and tumor microenvironment modulation. Journal of neuro-oncology Liu, J., Ha, J. H., Abikenari, M., Sjoholm, M. A., Annagiri, S., Ravi, K., Bergsneider, B. H., Verma, R., Theodros, D., Medikonda, R., Li, G., Prolo, L. M., Monje, M., Lim, M. 2025; 176 (2): 144

  Abstract

  Diffuse midline gliomas, including diffuse intrinsic pontine gliomas, represent one of the most aggressive pediatric malignancies in the central nervous system with a uniformly poor prognosis. They can be consistently identified by mutations in histone H3 K27M, which are associated with aggressive tumor biology, marked resistance to therapies, and abysmal survival. The current review critically assesses the existing application of immunotherapeutic modalities in DMGs, emphasizing biological hurdles in efficacy, translation methodologies, and prospects in attaining sustained responses.We examined preclinical and early clinical studies in DMGs for immune therapies such as peptide vaccines against H3K27M antigens, chimeric antigen receptor T-cell therapies, immune checkpoint modulation, and radioimmunotherapy. Current developments in the interface of cancer neuroscience and tumor interaction with neurons were incorporated in a manner relevant to immune suppression in the microenvironment of DMG. Although these tumors have traditionally shown poor immune reactivity because of low tumor mutational burden, immune-privileged sites, and a strongly suppressive tumor microenvironment, a variety of different immune therapeutic approaches have shown promising early efficacy. Of particular interest are neoantigen-targeted vaccines and CAR T-cell therapy using surface antigens. Preliminary findings suggest an important role for neuron-glioma synaptic and paracrine signaling in mediating tumor progression and immune evasion.Immunotherapy for DMGs is moving from a conceptual state to a translational reality. A better understanding of the realm of tumor immune-neural crosstalk, combination therapies, and immune biology in pediatric patients will be critical in addressing resistance and providing durable control for these aggressive malignancies.

  View details for DOI 10.1007/s11060-025-05347-9

  View details for PubMedID 41460355

  View details for PubMedCentralID 9533228

• Molecular and biophysical remodeling of the blood-brain barrier in glioblastoma: mechanistic drivers of tumor-neurovascular crosstalk FRONTIERS IN PHYSICS Abikenari, M., Sjoholm, M., Liu, J., Nageeb, G., Ha, J. H., Wu, J., Ren, A., Sayadi, J., Lim, J., Cho, K., Verma, R., Medikonda, R., Banu, M., Lim, M. 2025; 13

  View details for DOI 10.3389/fphy.2025.1723329

  View details for Web of Science ID 001651720600001

• Radiosurgical management of pathology-proven low-grade glioma: a systematic review across the pre- and post-molecular classification era. Journal of neurosurgical sciences Mizutani, Y., Hori, Y. S., Harary, P. M., Annagiri, S., Jain, R., Liu, J., Izhar, M., Reesh, D. A., Lam, F. C., Emrich, S. C., Ustrzynski, L., Tayag, A., Park, D. J., Chang, S. D. 2025

  Abstract

  Low-grade gliomas (LGGs) are slow-growing heterogeneous tumors that remain challenging when complete resection is not feasible. While maximal safe resection remains standard, the evolving World Health Organization (WHO) classification emphasizing molecular characteristics has shifted perspectives on adjuvant therapies. In this context, the role of stereotactic radiosurgery (SRS) continues to be explored. This systematic review synthesizes literature on radiosurgical management of pathology-proven LGGs across pre- and post-molecular classification eras.A systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses. PubMed, Scopus, and Web of Science were searched in August 2024 for studies on pathology-proven LGGs treated with SRS. An additional search was performed to incorporate studies reporting molecular characteristics.Of the initially included eight studies, none reported molecular characteristics required by the 2021 World Health Organization classification, and an additional search identified one study reporting molecular characteristics, which was added to the review. Nine studies with 308 patients were included. Local control rates ranged from 66% to 94%. Several studies reported superior outcomes with surgery for recurrence, adjuvant rather than salvage SRS, and no prior radiotherapy. Adverse events were predominantly mild to moderate, including headache, dizziness, nausea, and transient neurological symptoms.SRS offers a non-invasive management option for selected LGGs with durable control and acceptable safety. Prognosis appears to be influenced by treatment history, including prior radiotherapy and surgical management. Lack of molecular stratification highlights the need for studies focused on IDH (isocitrate dehydrogenase)-mutant LGGs to clarify the role of SRS in the molecular era.

  View details for DOI 10.23736/S0390-5616.25.06656-1

  View details for PubMedID 41364089

• The Acoustic Neuroma-7 Score: An Externally Validated Tool Predicting Facial Nerve Outcome After Vestibular Schwannoma Surgery. Neurosurgery Feghali, J., Reddy, S. C., Ahmed, A. K., Canales, M., Bhandarkar, S., Kramer, P., Ha, J., Liu, J., Kim, L. H., Vesole, A. S., Houssein, F., Galaiya, D., Ward, B., Boahene, K., Nellis, J., Chien, W., Della Santina, C. C., Francis, H., Creighton, F., Stewart, C. M., Carey, J., Xu, R., Caplan, J. M., Bettegowda, C., Weingart, J., Brem, H., Tamargo, R. J., Sun, D. Q., Lim, M., Jackson, C. M. 2025

  Abstract

  Externally validated scoring systems for facial nerve injury after vestibular schwannoma (VS) resection are lacking. We aimed to derive and externally validate a scoring system predictive of poor long-term facial nerve outcome after microsurgical resection of VS.Patients who underwent microsurgical resection of VS by a retrosigmoid approach at Johns Hopkins Hospital between July 2016 and April 2024 were included. An optimal stepwise multivariable logistic regression model predicting poor facial nerve outcome (House-Brackmann >2) at last follow-up was derived with a scoring system. Predictive metrics were compared with the previously published Facial Nerve Outcome Score (FNOS). An additional model using only preoperative factors was derived. External validation of accuracy and calibration was performed in Stanford Healthcare and University of Cincinnati Medical Center.In 360 VS patients, 80 patients (22%) experienced poor facial nerve outcome at last follow-up (3.1 ± 2.3 years). Gross total resection was achieved in 304 patients (84%). The optimal logistic regression model based on 316 patients with available data included abnormal renal function (odds ratio [OR] = 8.3, 95% CI [1.4-48.5], P < .001), neuroma size ≥2.2 cm (OR = 3.3, [1.7-6.6], P < .001), and stimulation threshold postresection (weak stimulation OR = 7.1, [3.1-16.2], P < .001). The 7-point acoustic neuroma score outperformed FNOS in our cohort (area under the receiver operating curve [AUC] = 0.807 [0.742-0.872] vs FNOS AUC = 0.696 [0.622-0.771], P < .001). Calibration plots showed excellent calibration. On external validation, AUCs of 0.713 [0.555-0.870] and 0.729 [0.547-0.911] were derived, with favorable calibration plots. A preoperative model excluding nerve stimulation threshold additionally performed well. A calculator was deployed at https://facialnervefunction.shinyapps.io/Facial_Nerve_Function_Calculator/.The acoustic neuroma 7 model can be used for patient counseling and for identifying high-risk patients for facial weakness while aiding in earlier referral for facial reanimation surgery.

  View details for DOI 10.1227/neu.0000000000003868

  View details for PubMedID 41342552

• Immune-Mediated Recurrent Glioblastoma Growth: Insights from a Novel Murine Model Schonfeld, E., Choi, J., Annagiri, S., Kim, L., Ha, J., Liu, J., Sjoholm, A., Lim, J., Lee, S., Lau, C., Cho, K., Verma, R., Lim, M. OXFORD UNIV PRESS INC. 2025: v219

  View details for DOI 10.1093/neuonc/noaf201.0867

  View details for Web of Science ID 001612030100009

• The immunological landscape of traumatic brain injury: insights from pathophysiology to experimental models. Frontiers in neurology Abikenari, M., Ha, J. H., Liu, J., Ren, A., Cho, K. B., Lim, J., Kim, L. H., Medikonda, R., Choi, J., Lim, M. 2025; 16: 1668480

  Abstract

  Traumatic brain injury (TBI) is a complex, heterogeneous neuropathological disease that continues to be among the prominent causes of mortality and disability around the world. Translational success in TBI has been significant, yet therapies are limited as the intersection of the initial mechanical traumas and secondary neuroinflammatory cascades, which predispose to long-term neurological deficits, is poorly understood. The pathogenesis of TBI is not limited to the primary mechanical injury. The secondary damage, including ischemia, excitotoxicity, oxidative stress, and immune dysfunction, leads to neuronal apoptosis, the breakdown of the blood-brain barrier (BBB), and chronic neuroinflammation. The preclinical controlled cortical impact (CCI) and fluid percussion injury (FPI) TBI models have generated valuable biomechanical data related to TBI-induced immune responses, including microglial priming, astrocyte dysregulation, and peripheral leukocyte recruitment. However, experimental models today are unable to completely replicate the intricate immune cascades in human TBI, particularly delayed and context-specific innate and adaptive immune response activation. Cytokine signaling (IL-1β, TNF-α, and IL-6), neuroinflammatory amplification through the IL-23/IL-17 pathway, and autoantibody-mediated neurodegeneration are emerging as significant secondary injury mechanisms. Additionally, TBI-induced immunosuppression, which presents as generalized T lymphocyte depletion and aberrant macrophage polarization, enhances the risk of infection and delayed neurological recovery. Emerging immunotherapeutics such as cytokine blockade, complement blockade, and targeted modulation of T lymphocytes have the potential to optimize the post-TBI immune microenvironment for reducing secondary damage. Inclusion of next-generation experimental models combined with secondary injuries, such as hypoxia, polytrauma, and systemic inflammation, is needed to shift towards innovative, biomarker-driven, patient-stratified trials. Thus, integration of immunological phenotyping with translationally relevant models of TBI represents an important cornerstone in the development of targeted therapeutic treatments designed to improve neuroprotection, repair, and long-term functional outcome.

  View details for DOI 10.3389/fneur.2025.1668480

  View details for PubMedID 41050281

  View details for PubMedCentralID PMC12488441

• Emerging trends in cell-based therapies: contemporary advances and ethical considerations in translational neurosurgical oncology. Journal of neuro-oncology Abikenari, M., Liu, J., Ha, J. H., Annagiri, S., Himic, V., Medikonda, R., Kim, L., Choi, J., Lim, M. 2025

  Abstract

  Emerging cell-based therapies represent a promising advancement in neurosurgical oncology, offering novel therapeutic possibilities for challenging diagnoses such as high-grade gliomas. Traditional treatment modalities, including surgical resection, chemotherapy, and radiotherapy, offer limited efficacy due to the highly infiltrative nature and genomic heterogeneity of malignant brain tumors. The recent integration of molecular profiling and genotypic characterization into diagnostic and therapeutic frameworks underscores a significant evolution toward personalized medicine. Stem-cell-based approaches, notably neural and mesenchymal stem cells, demonstrate remarkable tropism for pathological tissues, providing innovative strategies for targeted therapeutic delivery and intrinsic anti-tumoral effects. Concurrently, immunotherapeutic advancements, particularly immune checkpoint inhibitors (ICIs), chimeric antigen receptor T-cell (CAR T-cell) therapies, and tumor vaccination techniques, have significantly altered therapeutic paradigms by leveraging patient-specific immune responses with minimal systemic toxicity. To contextualize such therapeutic innovations, we systematically reviewed and analyzed 28 ongoing glioblastoma clinical trials initiated since 2022 investigating cell-based strategies. This dataset elucidates key patterns in trial design, cellular targets, and combinatorial immunotherapeutic regimens. Despite the immense clinical promise, integrating cell-based and immunological therapeutics necessitates careful ethical deliberation and complex clinical management strategies, particularly when combined with conventional therapies. This review critically evaluates contemporary advancements, highlights emerging clinical trial outcomes, explores the ethical dimensions of novel therapeutics, and underscores the imperative for continued translational research to refine patient-specific therapeutic paradigms in neurosurgical oncology.

  View details for DOI 10.1007/s11060-025-05170-2

  View details for PubMedID 40696259

  View details for PubMedCentralID 6889232