About

Elizabeth Olson Hexner, MD, MSTR, is an Associate Professor of Medicine (Hematology-Oncology) at the Hospital of the University of Pennsylvania and serves as the Associate Director of the MSTR program at the Perelman School of Medicine. She is also the Medical Director of the Center for Cellular Immunotherapies at the Perelman School of Medicine. Her research expertise includes genetically modified T cell therapies, CAR T cells, cellular therapy, blood and marrow transplantation, myeloproliferative neoplasms, and umbilical cord blood transplantation. Her educational background includes a premedical studies at Harvard University Extension School, an MD from Columbia College of Physicians and Surgeons, and a MSTR in Translational Research from the University of Pennsylvania. She has contributed to the field through her involvement in research on targeted T-cell therapies and immunotherapies for hematologic malignancies.

Research topics

• Immunology
• Medicine
• Internal medicine
• Cancer research
• Oncology
• Pharmacology
• Biology
• Genetics
• Chemistry
• Pathology
• Bioinformatics
• Surgery
• Computational biology

Selected publications

• Abstract 3444: Spatial profiling of recurrent glioblastoma in a Phase I clinical trial reveals favorable immune remodeling induced by intracerebroventricular CAR T therapy

  Cancer Research · 2026-04-03

  article

  Abstract Recurrent glioblastoma (rGBM) is an aggressive brain tumor with median survival under one year after standard chemoradiation. Antigen heterogeneity, immune exclusion, and a suppressive tumor microenvironment (TME) limit responses to immunotherapy. A first-in-human phase 1 trial of intracerebroventricular EGFR/IL13Rα2 CAR T cells (CART-EGFR-IL13Rα2) in EGFR-amplified rGBM was feasible, produced manageable neurotoxicity, and induced radiographic tumor regressions in a subset of patients (NCT05168423).To understand how this therapy reshapes the local TME, we analyzed paired tumor resections from 6 patients enrolled in the phase 1 trial, with specimens obtained from the primary intracranial disease site at trial enrollment (pre-treatment) and at radiographic progression after CART-EGFR-IL13Rα2 infusion. Multimodal spatial profiling included regional transcriptomic and protein mapping (GeoMx), single-cell whole-transcriptome imaging (CosMx), and high-resolution spatial transcriptomics (Visium HD). We annotated tumor, myeloid, lymphoid, and stromal compartments and derived composite scores for stemness, invasion, cell death, and immune regulation. Neighborhood- and interaction-based analyses were used to compare cellular states and cell-cell communication.Across patients, post-treatment samples showed reduced expression of CAR target antigen and a shift in tumor-intrinsic programs toward less stem-like, less migratory, and more apoptotic states, despite radiographic progression. The post-treatment TME was remodeled, with fewer suppressive myeloid- and B-cell-rich niches and increases in interferon-responsive and T cell-associated activation programs. Spatial interaction analyses indicated that pre-treatment rGBM contained dense networks of myeloid-tumor and myeloid-T-cell contacts consistent with impaired antigen presentation and effector function. Post-treatment specimens, in contrast, showed partial disruption of these suppressive circuits and the emergence of microenvironments more permissive to T-cell infiltration and activity.In the parent phase 1 trial, CART-EGFR-IL13Rα2 was feasible & induced radiographic tumor regressions in a subset of patients. This correlative spatial analysis suggests that prior EGFR/IL13Rα2 CAR T exposure can leave a less suppressive, more immunologically engaged TME at the primary site, even in resections obtained at radiographic progression. Together, these data support the idea that intracerebroventricular CAR T therapy may condition rGBM for subsequent immunotherapy. Myeloid and B-cell interactions are highlighted as candidate targets for armoring next-generation CAR T cells and for designing rational combination and sequencing strategies. Citation Format: Wesley V. Wilson, MacLean P. Nasrallah, Nakial Cross, Yael A. Day, Vanessa Gonzalez, Rachel M. Leskowitz, Amy Marshall, Julie K. Jadlowsky, Gabriela Plesa, Donald L. Siegel, Elizabeth O. Hexner, Joseph A. Fraietta, Carl H. June, Stephen J. Bagley, Donald O’Rourke, Zev Binder, Andrew J. Rech. Spatial profiling of recurrent glioblastoma in a Phase I clinical trial reveals favorable immune remodeling induced by intracerebroventricular CAR T therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3444.

  PublisherDOI

• Systemic steroid treatment of grade I acute GVHD increases steroid-refractory GVHD and NRM

  Blood Immunology & Cellular Therapy · 2026-03-24

  articleOpen access

  = .026). MAGIC biomarkers identified most patients with grade I GVHD as low risk and unlikely to progress to severe GVHD regardless of treatment. Nevertheless, low-risk patients who received up-front steroids experienced a threefold increase in infectious deaths compared with those treated topically. This study supports the consensus recommendation of topical therapy for patients with low-risk grade I GVHD, a strategy that can be supported by biomarkers to avoid unnecessary steroid exposure and increased NRM.

  PublisherDOI

• Cytotoxic, natural killer-like ex-tissue resident memory T-cells circulate in human chronic graft-versus-host disease at diagnosis

  Blood · 2025-11-03

  articleOpen access

  Abstract Emerging evidence implicates tissue resident memory T-cells (TRM) in chronic graft-versus host disease (cGVHD) immunopathology. While traditionally considered confined to tissues, recent studies indicate TRM can re-enter the circulation as “ex-TRM” in inflammatory conditions. However, the role of ex-TRM in cGVHD, and the link between peripheral blood (PB) and tissue-based immunopathology in cGVHD are not well understood. To identify and characterize ex-TRM in cGVHD, we utilized 10X Genomics 5' GEM-X technology to perform single-cell RNA sequencing (scRNA-Seq) and single-cell TCR sequencing (scTCR-Seq) on T-cell selected PBMC samples from patients with newly diagnosed, treatment-naive cGVHD (n=8) and post-allogeneic stem cell transplant (ASCT) matched controls (MC; n=5) who did not develop relapse or acute/chronic GVHD. Quality control (QC), normalization, clustering, principal component analysis, dimensionality reduction, and integration were performed with Seurat v5.2.1 in R v4.4.2. CD8+ effector memory (EM) subsets were re-clustered to enhance resolution for ex-TRM. TCR clonality was assessed in ScRepertoire, and antigen specificity was determined for alpha/beta TCR amino acid sequences using ImmuneWatch DETECT. Differences in continuous variables were assessed using the Wilcoxon rank-sum test, and Bonferroni correction was applied for differential gene expression (DGE) analysis. Significance was set at p < 0.05 All patients received matched donor transplants and tacrolimus and methotrexate for GVHD prophylaxis. There were no significant differences between cGVHD and MC for age, sex, donor type (related vs. unrelated), CMV serostatus, conditioning regimen, or sample timepoint post-ASCT. After QC, 29,107 CD8+ T-cells (17,938 cGVHD and 11,1169 MC) were analyzed. Re-clustering of CD8+ EM cells revealed a distinct cluster expressing canonical TRM markers (CXCR6, ITGA1, ITGAE, CD69) as well as TRM-associated genes CXCL13 and CRTAM, consistent with ex-TRM. To further validate the TRM-like signature, we performed cluster-based module scoring using: 1) the top 100 upregulated genes from our recent publication in TRM vs. non-TRM in explanted lung tissue from pulmonary cGVHD and 2) the top 200 upregulated genes from an external dataset comparing lung TRM to circulating EM T-cells in healthy controls. Module scores for both gene sets were highest in the ex-TRM cluster, confirming TRM-like identity. The ex-TRM cluster included all cGVHD patients and MC in similar proportions. We then compared abundance and gene expression of ex-TRM in cGVHD patients and MC. Ex-TRM as a fraction of CD8+ EM was similar between groups (0.08 vs 0.09). However, cGVHD ex-TRM showed upregulation of cytotoxicity genes (GZMB, GNLY, PRF1), NK-like (NKL) markers (KLRD1, FGFBP2, NKG7), and T-cell exhaustion (Tex)-associated genes (DUSP4, HAVCR2). The median module score for an external Tex gene signature was higher in cGVHD than MC (0.029 vs 0.016, p <0.001). DGE results were consistent after stratification by CMV serostatus. TCR analysis showed similar proportions of hyperexpanded (>100 cells/clonotype) and large (20-100 cells/clonotype) clones in ex-TRM between conditions (30% versus 28%). Normalized entropy scores for ex-TRM were identical (0.92), indicating comparable repertoire diversity. However, hyperexpanded and large clones in cGVHD exhibited even greater upregulation of cytotoxicity, NKL, and Tex genes by log2 fold change than the overall ex-TRM population. Finally, ImmuneWatch DETECT did not find viral epitope-specific clonotypes in ex-TRM from cGVHD patients, suggesting that expansion may reflect alloantigen recognition. In conclusion, we identified circulating ex-TRM during post-ASCT immune reconstitution using canonical TRM markers and module scoring. In cGVHD, ex-TRM had a distinct cytotoxic, NKL, and Tex gene signature, supporting possible antecedent tissue antigen exposure and pathogenicity. Future work will explore protein level validation and assess phenotypic and clonal overlap between ex-TRM and bona fide TRM in affected tissues. With further validation, ex-TRM may provide a surrogate for tissue-resident populations and the foundation for non-invasive biomarkers in cGVHD.

  PublisherOA PDFDOI

• Figure S6 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T Cell–Intrinsic Dysfunction

  2025-12-11

  articleOpen access

  <p>Pathways regulated by EGR2 in CD8+ CAR T-cells. (A-C) Top pathways differentially expressed in EGR2 knockout CD8+ CAR-T cells compared to AAVS1 knockout CAR T-cells. Libraries used in this enrichment analysis: A, Reactome 2016. B, NCI-Nature Pathway Interaction Database 2015. C, ARCHS4 transcription factor (TF) co-expression.</p>

  PublisherOA PDFDOI

• Figure S11 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T Cell–Intrinsic Dysfunction

  2025-12-11

  articleOpen access

  <p>Analysis of survival outcomes and EGR2 gene expression in CD19 CAR T-cell products. The figure presents the P values and hazard ratio of different EGR2 molecular marker stratification points in relation to A, overall survival and B, event-free survival The black arrows indicate the stratification points used in the study. C, EGR2-targeted gene expression scores in CD19 CAR T-cell products from responders and non-responders in pediatric ALL. D, Summary of how EGR2 regulates resistance to CAR T-cell therapy through the type I IFN pathway.</p>

  PublisherOA PDFDOI

• Supplementary Tables and Figures from Anti-BCMA/CD19 CAR T Cells with Early Immunomodulatory Maintenance for Multiple Myeloma Responding to Initial or Later-Line Therapy

  2025-11-24

  articleOpen access

  <p>Supplemental tables: (1) Subject characteristics. (2) Cytogenetic profiles and high-risk features. (3) Prior treatment exposures and refractoriness. (4) CAR T cell product characteristics. (5) Products that did not meet target dose. (6) Adverse events of grade 3-4. (7) Cytokine release syndrome and ICANS. (8). Maintenance therapy. Supplemental Figures: (1) Study schematic and subject disposition, (2) Correlates of manufacturing success, (3) Hematopoietic recovery, (4) Post-infusion T cell phenotypes, (5) Correlates of in vivo expansion and manufacturing success, (6) Late post-infusion CAR T cell re-expansion, (7) Soluble BCMA, (8) Late-onset clinical responses, (9) MM cell BCMA expression, (10) Pre- and post-treatment Sox2-specific T cell responses in CART-BCMA monotherapy patients, (11) Pre- and post-treatment Sox2-specific T cell responses in CART-BCMA + huCART19 combination therapy patients, (12) Sustained post-treatment SOX2-specific T-cell responses.</p>

  PublisherDOI

• Table S2 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T Cell–Intrinsic Dysfunction

  2025-12-11

  articleOpen access

  <p>Genes deferentially expressed in EGR2 compared to AAVS1 knockout CD8+ CAR T-cells. The corresponding log2 fold change values and statistical significance are provided for the listed genes.</p>

  PublisherDOI

• Figure S5 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T Cell–Intrinsic Dysfunction

  2025-12-11

  articleOpen access

  <p>Gene expression and pathway enrichment analysis of CD8+ T cell clusters. A, Heatmap showing differentially expressed genes between memory-like KLF2+ and exhausted-like MKI67+ CD8+ T-cells. Gene signature scores related to cell cycle and clinical response are indicated on the top bars. B, Top downregulated GO biological processes in EGR2 compared to AAVS1 knockout CAR T-cells.</p>

  PublisherDOI

• Grade I acute graft-vs-host disease: Treat or not?

  Blood · 2025-11-03

  article

  Abstract Background Acute graft-versus-host disease (GVHD) is a major cause of non-relapse mortality (NRM) after allogeneic hematopoietic cell transplantation (HCT). High-dose steroids are standard first-line therapy for grade II–IV acute GVHD, whereas systemic treatment (tx) is generally not recommended for grade I. However, in practice many patients (pts) with grade I GVHD receive systemic steroids. A prior GITMO randomized trial (n=173) of grade I GVHD to either systemic steroid tx or “watch and wait” found that preemptive steroid tx reduced progression to grade II but not grade III/IV GVHD, increased serious infections, and resulted in similar chronic GVHD, NRM and survival (Bacigalupo, Haematologica 2017). In this study we analyzed real world evidence for early systemic steroid use and the potential impact of serum biomarkers in grade I GVHD. Methods We analyzed clinical data and serum samples from pts with grade I acute GVHD at 24 Mount Sinai Acute GVHD International Consortium (MAGIC) centers between 2014 and 2022 who were treated according to physician discretion. Pts were divided into a preemptive steroid tx group or a watch-and-wait group (systemic steroids administered only if progression to grade II–IV GVHD). Preemptive steroid use was treated as a time-dependent covariate and a frailty proportional hazards model with random effects was used to adjust for center effects to account for possible heterogeneity in clinical practices across transplant centers. Serum samples collected at the diagnosis of grade I GVHD were analyzed for ST2 and REG3α to calculate validated Ann Arbor (AA) scores (1, 2, 3). Results Grade I GVHD was diagnosed in 1143 pts; 591 (52%) received preemptive tx and 552 (48%) were treated by a watch-and-wait strategy. In the preemptive tx group, steroids were initiated at a median of 0 days and within 7 days for >90%. The median initial dose of steroids was 1 mg/kg of prednisone or its equivalent. In the watch and wait group, only 184 pts (33%) required systemic steroids for progression to grade II-IV GVHD at a median of 14 days from grade I diagnosis. Preemptive steroid tx reduced the risk of grade II–IV acute GVHD (HR, 0.71; 95% CI, 0.56–0.89; P=0.003), but not the risk of grade III/IV acute GVHD (HR, 1.03; 95% CI, 0.69–1.52; P=0.899) or chronic GVHD (HR, 1.03; 95% CI, 0.69–1.52; P=0.899), consistent with the GITMO trial. The 12-month incidence of NRM was higher for preemptive tx vs. watch and wait (13% vs 7%, P=0.002). In multivariate analysis preemptive steroid use independently predicted an increased risk of NRM (HR, 1.63; 95% CI, 1.06–2.50; P=0.026) as did several other known risk factors (older recipient age, umbilical cord blood donor, HCT-CI ≥3, and myeloablative conditioning). Greater NRM in the preemptive tx group was driven primarily by 3-fold more infectious deaths; deaths due to uncontrolled GVHD were similar for both tx groups. The risk for relapse was unexpectedly lower in the preemptive tx group (HR 0.64; 95% CI 0.47-0.88; P=0.006) and overall survival was therefore not different between groups, but risk factors for relapse such as minimal residual disease status were not available precluding further analysis of this finding. Serum was collected in 871 (76%) pts at onset of grade I GVHD for retrospective biomarker analysis. AA scores were AA1 (80%), AA2 (15%), and AA3 (5%). AA scores were highly predictive of progression to grade III/IV GVHD (AA1 vs AA2 vs AA3: 9% vs 14% vs 44%, all P<0.001) and the risk of 12-month NRM (8% vs 16% vs 39%, all P<0.001); this pattern was observed in both tx groups. The negative effect of preemptive steroid tx was most pronounced in pts with grade I/AA1 GVHD who experienced 5-fold more infectious related deaths compared to pts managed with a watch and wait approach. Conclusion Treatment of grade I GVHD with systemic steroids did not reduce the incidence of grade III/IV GVHD or deaths due to uncontrolled GVHD and instead increased the risk of NRM from infections compared to pts who were treated only after GVHD progressed. Importantly, 2/3 of the watch and wait pts never needed systemic steroid tx. These findings remained robust after adjusting for multiple confounders, including center effects, and were consistent with the GITMO trial. MAGIC biomarkers at the onset of grade I GVHD predicted outcomes and a watch and wait strategy may be best for the 80% of pts with AA1 GVHD. Better treatment options are needed for the 20% of pts with grade I and AA2/3 GVHD.

  PublisherDOI

• Figure S9 from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T Cell–Intrinsic Dysfunction

  2025-12-11

  articleOpen access

  <p>Epigenetic remodeling of CAR T-cells by EGR2 knockout and effect of type I IFN signaling on the development of memory and exhaustion. A, Volcano plots showing differentially accessible chromatin regions within genes between KLF2+ and MKI67+ CD8+ T-cells. B, Volcano plots depicting differentially accessible chromatin regions within genes between EGR2 and AAVS1 knockout (KO) CD8+ CAR T-cells. C, Representative contour plots showing frequencies of TIM3- and LAG3-expressing CD8+ CAR-T cells after exposure to IFNβ (1ng/mL) following chronic CAR stimulation. D, Proportions of CD27+ (left) or CD62L+ (right) CD8+ CAR-T cells after exposure to IFNβ. E, Representative contour plots showing frequencies of CD45RO+CD27+ CD8+ CAR-T cells after IFNAR blockade (Anifrolumab, 1µg/mL) during chronic antigen stimulation. F, Frequencies of TIM3+LAG3+ CD8+ CAR-T cells after IFNAR blockade. G, Cytolytic capacity of CAR T-cells as measured by normalized cell index kinetics using the xCELLigence real-time cytotoxicity assay following chronic stimulation with target cancer cells in the setting of either IFNβ or IFNAR blockade. H, Normalized cell index at 75 hours after challenge with target cancer cells. All experiments were conducted using healthy donor T-cells from independent donors (Mann-Whitney test, n = 4). *P < 0.05, *P < 0.01, ***P < 0.001, ns.: not significant.</p>

  PublisherOA PDFDOI

Recent grants

• NIH Grant K23HL093366

  NIH · $412k · 2015

• NIH Grant K23HL09336601A1

  NIH · $137k · 2013

Frequent coauthors

• Noelle V. Frey

  California University of Pennsylvania

  199 shared

• Jason Gotlib

  Incyte (United States)

  160 shared

• David L. Porter

  University of Pennsylvania

  154 shared

• Tracy I. George

  Cogent Biosciences (United States)

  135 shared

• Aaron T. Gerds

  Cleveland Clinic

  128 shared

• Joseph A. Fraietta

  University of Pennsylvania

  116 shared

• Sanjay Mohan

  Breast Cancer Research Foundation

  113 shared

• Krishna Gundabolu

  University of Nebraska at Omaha

  113 shared