About

Dr. Christina Jackson is an Assistant Professor of Neurosurgery at the Hospital of the University of Pennsylvania, affiliated with the Perelman School of Medicine. She specializes in open skull base surgery, minimally invasive surgery, endoscopic skull base and pituitary surgery, and complex brain tumor surgery. Her clinical expertise includes the treatment of benign and malignant brain tumors, with a particular focus on skull base tumors such as pituitary adenomas, meningiomas, craniopharyngiomas, chordomas, chondrosarcomas, schwannomas, and esthesioneuroblastomas. Dr. Jackson received her medical degree from Harvard Medical School and completed her neurosurgery residency at Johns Hopkins University School of Medicine. She further specialized through a fellowship at the University of Pittsburgh Medical Center, focusing on endoscopic endonasal and open skull base surgical techniques. Her training in both open and endoscopic approaches allows her to select the most effective and less invasive surgical methods tailored to each patient. Her research interests lie at the intersection of immunology, metabolism, and brain tumor biology, aiming to understand mechanisms of immune evasion by primary malignant brain tumors and skull base tumors to develop novel immune-based therapies. Her lab employs high-dimensional immune and genomic profiling, metabolomics, and advanced tumor models to investigate immune cell function within the tumor microenvironment, including the roles of myeloid-derived suppressor cells, T cell exhaustion, and metabolic networks.

Research topics

• Medicine
• Immunology
• Cancer research

Selected publications

• The effect of TERT promoter mutation on predicting meningioma outcomes: a multi-institutional cohort analysis

  The Lancet Oncology · 2025-09-01 · 11 citations

  articleOpen access
  PublisherOA PDFDOI

• Deciphering Cell Fate and Clonal Dynamics via Integrative Single-Cell Lineage Modeling

  Research Square · 2025-09-24

  preprintOpen accessSenior author
  PublisherOA PDFDOI

• The Impact of TERT Promoter Mutation on Meningioma Outcome is Context-Dependent: Implications for Clinical Grading and Risk Stratification

  SSRN Electronic Journal · 2025-01-01

  preprintOpen access
  PublisherDOI

• Rate of biopsy prior to resection among patients with high-grade glioma: a nationwide database analysis

  Journal of neurosurgery · 2025-11-08

  article

  OBJECTIVE: In cases of high-grade glioma that ultimately proceed to resection, a purely diagnostic biopsy might be unnecessary and add undue risk and cost. The frequency of resection following biopsy in a short time frame has not been reported among patients with high-grade glioma using a nationwide database. The objective of this study was to determine the occurrence rate of resection within 60 days of biopsy among patients with high-grade glioma and to determine if this occurrence is associated with patient or hospital characteristics. METHODS: This retrospective cohort study used a large private health insurance database to identify adult patients who underwent craniotomy for resection of high-grade glioma and received radiation treatment and temozolomide within 90 days of surgery from 2006 to 2022. This patient cohort was also queried for patients who underwent surgery for biopsy within the 60 days preceding craniotomy. The patient and hospital-related factors associated with biopsy within 60 days prior to resection were then examined. RESULTS: A total of 3051 patients who underwent resection of high-grade glioma were included; 106 patients (3.5%) underwent additional surgery for biopsy within 60 days prior to resection. The likelihood of undergoing additional surgery for biopsy prior to resection decreased with increasing age (in 5-year increments, OR 0.93 [95% CI 0.87-0.99]; p = 0.04). Patients who underwent biopsy were significantly younger (p = 0.02). The Northeast region had the highest rate of preresection biopsies (4.1%, 11/267). Most patients (93.1%, 94/101) underwent preresection biopsy at non-high-volume centers, and 24.5% (23/94) of these patients subsequently underwent resection at a high-volume center. CONCLUSIONS: A low proportion of patients with high-grade glioma underwent additional surgery for biopsy prior to resection. This finding provides a baseline as preresection biopsy might become more common in the context of investigational drug development requiring pretreatment baseline specimens.

  PublisherDOI

• Combined transorbital neuroendoscopic and endoscopic endonasal resection of orbital hemangioma

  Neurosurgical Focus Video · 2025-04-01

  articleOpen access1st authorCorresponding

  Orbital cavernous hemangiomas are the most common benign primary neoplasm of the orbit in adults and can lead to proptosis and optic neuropathy. Resection is the primary treatment for symptomatic cases. Choice of surgical approach depends on the lesion's size, location, and relation to intraorbital structures. The authors present the case of a 40-year-old male with a large symptomatic orbital hemangioma resected through a combined endoscopic transorbital and endonasal approach. This case highlights the advantages of the combined approach, enhancing visibility and minimizing disruption of orbital structures, allowing for en bloc resection of large orbital hemangiomas. The video can be found here: https://stream.cadmore.media/r10.3171/2025.1.FOCVID24197.

  PublisherOA PDFDOI

• Deciphering Cell Fate and Clonal Dynamics via Integrative Single-Cell Lineage Modeling

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-09-04 · 1 citations

  preprintOpen access

  Through natural or synthetic lineage barcodes, single-cell technologies now enable the joint measurement of molecular states and clonal identities, providing an unprecedented opportunity to study cell fate and dynamics. Yet, most computational methods for inferring cell development and differentiation rely exclusively on transcriptional similarity, overlooking the lineage information encoded by lineage barcodes. This limitation is exemplified by T cells, where subtle transcriptional differences mark divergent fates with distinct biological activity. Single-cell RNA and matched TCR sequencing is now ubiquitous in the analysis of clinical samples, where the TCR sequence provides an endogenous clonal barcode and could reveal clonal T cell responses. We present Clonotrace, a computational framework that jointly models gene expression and clonotype information to infer cell state transitions and fate biases with higher fidelity. While motivated by challenges in analyzing T cell populations, especially in the tumor microenvironment and immunotherapy settings, Clonotrace is broadly applicable to any lineage-barcoded single-cell dataset. Across diverse systems including T cells, hematopoietic differentiation, and cancer therapy resistance models, Clonotrace reveals differentiation hierarchies, distinguishes unipotent from multipotent states, and identifies candidate fate-determining genes driving lineage commitment.

  PublisherOA PDFDOI

• CTIM-37. DUAL CHECKPOINT BLOCKADE WITH ANTI-PD-1 AND ANTI-LAG-3 DRIVES EXPANSION AND EXHAUSTION OF GZMK+ TUMOR-REACTIVE T CELL CLONES IN GLIOBLASTOMA

  Neuro-Oncology · 2025-11-01

  articleOpen accessSenior author

  Abstract INTRODUCTION Despite the lack of efficacy with immune checkpoint inhibitors (ICIs) in glioblastoma, there is evidence that neoadjuvant ICI impacts the glioblastoma tumor microenvironment and promotes survival in subsets of patients. Given the non-redundant mechanisms of T cell dysfunction mediated by different checkpoints, there is growing interest in combining ICIs for added efficacy. However, the immune responses of patients receiving dual ICIs, specifically anti-PD-1 and anti-LAG-3, remain poorly understood. Objective: We aimed to determine the impact of combination ICIs on glioblastoma T-cell landscape to elucidate determinants of immunotherapy response and resistance. METHODS We performed single-cell RNA and paired TCR sequencing on tumor infiltrating lymphocytes from 27 IDH-wildtype glioblastoma patients (22 treatment-naïve; 5 treated with dual ICIs). RESULTS We found that the most clonally expanded population of T cells in glioblastoma consisted of developmentally plastic GZMK+ T cells that are capable of diverging into three distinct states: GZMK+ resident T cells, terminal effector/dysfunctional T cells, and T cells re-expressing CD45RA. Our results revealed a paucity of putative tumor-reactive T cell clones in untreated glioblastoma patients. Treatment with dual ICIs recruits novel tumor-reactive T cell clones from the periphery and drives GZMK+ T cells toward an effector and dysfunctional trajectory along an exhaustion gradient characterized by upregulated TCR signaling, antigen presentation, proliferation, and multiple checkpoints. CONCLUSIONS Our work identifies a population of GZMK+ effector memory T cells as the primary target of dual ICIs in glioblastoma with tumor-reactive T cells almost exclusively present in this transitional population. Dual ICI recruits novel T cell clones from the peripheral and preferentially activates GZMK+ T cells toward terminal effector and dysfunctional states. Our findings provide key mechanistic insights into how dual ICIs reshapes the T cell landscape and repertoire in glioblastoma and identify potential mechanisms of immunotherapy resistance, highlighting opportunities for therapeutic optimization.

  PublisherOA PDFDOI

• Development and Characterization of a Primary Patient Tumor Tissue-Derived Skull-Base Chordoma Organoid Model

  Journal of Neurological Surgery Part B Skull Base · 2025-02-01

  article
  PublisherDOI

• Dual checkpoint blockade of glioblastoma with Anti-PD-1 and Anti-LAG-3 promotes expansion of tumor-reactive T cell clones along a unique pathway of differentiation

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-09-11 · 2 citations

  preprintOpen accessSenior authorCorresponding

  ABSTRACT IDH-wildtype grade IV glioblastoma is the most aggressive adult primary brain tumor and remains refractory to anti-PD-1 monotherapy despite evidence of limited tumor-specific T cell induction. To determine the impact of immune checkpoint inhibitors (ICIs) on glioblastoma T cell transcriptional landscape and repertoire, we conducted paired single-cell RNA sequencing (scRNA-seq) and T cell receptor sequencing (TCR-seq) of tumor-infiltrating lymphocytes (TILs) from patients with untreated, newly diagnosed glioblastoma and from recurrent glioblastoma treated with dual checkpoint blockade targeting PD-1 and LAG-3. Using a validated transcriptional signature, we found that predicted tumor-reactive T cells (TRC) in untreated glioblastomas reside almost exclusively in a clonally expanded GZMK hi population with developmental plasticity, affording them the potential to differentiate into both tissue-resident and terminal effector T cells. Dual ICI therapy induced substantial clonal remodeling, characterized by the recruitment of new TRC from the periphery into the tumor microenvironment (TME) and differentiation into transitional effectors and ultimately terminal effectors along a gradient characterized by simultaneous acquisition of cytotoxic and exhaustion genes, regulated by specific transcriptional, metabolic, and epigenetic programs. Longitudinal clonal tracking in peripheral blood confirmed that with ICI treatment, most TRC expand transiently in circulation prior to tumor infiltration, with peripherally derived clones becoming the major contributor to the GZMK hi TRC that further expand in the tumor. Our study provides the first comprehensive map of T cell clonal dynamics and differentiation in glioblastoma following dual ICIs and highlights a potential mechanism of immune activation and peripheral recruitment of TRC in glioblastoma not previously described. Our results suggest that therapeutic strategies to sustain these GZMK hi early effector and transitional effector T cells may further enhance ICI therapeutic efficacy in glioblastoma.

  PublisherOA PDFDOI

• Distinct myeloid-derived suppressor cell populations in human glioblastoma

  Science · 2025-01-16 · 83 citations

  articleOpen access1st authorCorresponding

  The role of glioma-associated myeloid cells in tumor growth and immune evasion remains poorly understood. We performed single-cell RNA sequencing of immune and tumor cells from 33 gliomas, identifying two distinct myeloid-derived suppressor cell (MDSC) populations in isocitrate dehydrogenase-wild-type (IDT-WT) glioblastoma: an early progenitor MDSC (E-MDSC) population with up-regulation of metabolic and hypoxia pathways and a monocytic MDSC (M-MDSC) population. Spatial transcriptomics demonstrated that E-MDSCs geographically colocalize with metabolic stem-like tumor cells in the pseudopalisading region. Ligand-receptor analysis revealed cross-talk between these cells, where glioma stem-like cells produce chemokines attracting E-MDSCs, which in turn produce growth factors for the tumor cells. This interaction is absent in IDH-mutant gliomas, associated with hypermethylation and repressed gene expression of MDSC-attracting chemokines. Our study elucidates specific MDSCs that may facilitate glioblastoma progression and mediate tumor immunosuppression.

  PublisherOA PDFDOI

Frequent coauthors

• Michael Lim

  Stanford University

  92 shared

• Kaisorn L. Chaichana

  WinnMed

  75 shared

• Jefferson W. Chen

  University of California, Irvine

  49 shared

• Ben A. Strickland

  49 shared

• Drew M. Pardoll

  Johns Hopkins University

  49 shared

• Gustavo Pradilla

  Emory University

  49 shared

• Julian E. Bailes

  NorthShore University HealthSystem

  49 shared

• Ronald L. Young

  Cleveland Clinic

  49 shared