Eda Holl

Positions:

Adjunct Assistant Professor in the Department of Surgery

Surgery, Surgical Sciences
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

Ph.D. 2010

University of North Carolina - Chapel Hill

Grants:

Retrospective Review Evaluating the PSA Changes in Patients with Metastatic Castrate Resistant Prostate Cancer after Sipuleucel-T treatment

Administered By
Duke Cancer Institute
Awarded By
Dendreon Corporation
Role
Principal Investigator
Start Date
End Date

Tumor draining lymph node B cells as regulators of melanoma progression

Administered By
Surgery, Surgical Sciences
Awarded By
Department of Defense
Role
Principal Investigator
Start Date
End Date

Publications:

Characterization of Sentinel Lymph Node Immune Signatures and Implications for Risk Stratification for Adjuvant Therapy in Melanoma.

BACKGROUND: Although sentinel lymph node (SLN) biopsy is a standard procedure used to identify patients at risk for melanoma recurrence, it fails to risk-stratify certain patients accurately. Because processes in SLNs regulate anti-tumor immune responses, the authors hypothesized that SLN gene expression may be used for risk stratification. METHODS: The Nanostring nCounter PanCancer Immune Profiling Panel was used to quantify expression of 730 immune-related genes in 60 SLN specimens (31 positive [pSLNs], 29 negative [nSLNs]) from a retrospective melanoma cohort. A multivariate prediction model for recurrence-free survival (RFS) was created by applying stepwise variable selection to Cox regression models. Risk scores calculated on the basis of the model were used to stratify patients into low- and high-risk groups. The predictive power of the model was assessed using the Kaplan-Meier and log-rank tests. RESULTS: During a median follow-up period of 6.3 years, 20 patients (33.3%) experienced recurrence (pSLN, 45.2% [14/31] vs nSLN, 20.7% [6/29]; p = 0.0445). A fitted Cox regression model incorporating 12 genes accurately predicted RFS (C-index, 0.9919). Improved RFS was associated with increased expression of TIGIT (p = 0.0326), an immune checkpoint, and decreased expression of CXCL16 (p = 0.0273), a cytokine important in promoting dendritic and T cell interactions. Independent of SLN status, the model in this study was able to stratify patients into cohorts at high and low risk for recurrence (p < 0.001, log-rank). CONCLUSIONS: Expression profiles of the SLN gene are associated with melanoma recurrence and may be able to identify patients as high or low risk regardless of SLN status, potentially enhancing patient selection for adjuvant therapy.
Authors
Farrow, NE; Holl, EK; Jung, J; Gao, J; Jung, S-H; Al-Rohil, RN; Selim, MA; Mosca, PJ; Ollila, DW; Antonia, SJ; Tyler, DS; Nair, SK; Beasley, GM
MLA Citation
Farrow, Norma E., et al. “Characterization of Sentinel Lymph Node Immune Signatures and Implications for Risk Stratification for Adjuvant Therapy in Melanoma.Ann Surg Oncol, vol. 28, no. 7, July 2021, pp. 3501–10. Pubmed, doi:10.1245/s10434-020-09277-w.
URI
https://scholars.duke.edu/individual/pub1465295
PMID
33205334
Source
pubmed
Published In
Annals of Surgical Oncology
Volume
28
Published Date
Start Page
3501
End Page
3510
DOI
10.1245/s10434-020-09277-w

Controlling cancer-induced inflammation with a nucleic acid scavenger prevents lung metastasis in murine models of breast cancer.

Tumor cells release nucleic acid-containing proinflammatory complexes, termed nucleic acid-containing damage-associated molecular patterns (NA DAMPs), passively upon death and actively during stress. NA DAMPs activate pattern recognition receptors on cells in the tumor microenvironment leading to prolonged and intensified inflammation that potentiates metastasis. No strategy exists to control endogenous or therapy-induced inflammation in cancer patients. We discovered that the generation 3.0 polyamidoamine dendrimer (PAMAM-G3) scavenges NA DAMPs and mitigates their proinflammatory effects. In this study, we tested if the nucleic acid scavenger (NAS) PAMAM-G3 reduces lung metastasis in murine models of breast cancer. Our data indicate that PAMAM-G3 treatment decreases cell-free DNA levels and reduces lung metastasis in the experimental intravenous tumor-injection model and the postsurgical tumor-resection model of 4T1 breast cancer. Reduction in lung metastasis is associated with reduction in inflammatory immune cell subsets and proinflammatory cytokine levels in the tumor and the periphery. This study is the first example of NAS-mediated inhibition of metastasis to the lung. The study results provide a strong rationale for inclusion of NAS therapy in women with breast cancer undergoing standard-of-care surgery.
Authors
Holl, EK; Frazier, V; Landa, K; Boczkowski, D; Sullenger, B; Nair, SK
MLA Citation
Holl, Eda K., et al. “Controlling cancer-induced inflammation with a nucleic acid scavenger prevents lung metastasis in murine models of breast cancer.Mol Ther, vol. 29, no. 5, May 2021, pp. 1772–81. Pubmed, doi:10.1016/j.ymthe.2020.12.026.
URI
https://scholars.duke.edu/individual/pub1469984
PMID
33348055
Source
pubmed
Published In
Molecular Therapy : the Journal of the American Society of Gene Therapy
Volume
29
Published Date
Start Page
1772
End Page
1781
DOI
10.1016/j.ymthe.2020.12.026

Viral infection of cells within the tumor microenvironment mediates antitumor immunotherapy via selective TBK1-IRF3 signaling.

Activating intra-tumor innate immunity might enhance tumor immune surveillance. Virotherapy is proposed to achieve tumor cell killing, while indirectly activating innate immunity. Here, we report that recombinant poliovirus therapy primarily mediates antitumor immunotherapy via direct infection of non-malignant tumor microenvironment (TME) cells, independent of malignant cell lysis. Relative to other innate immune agonists, virotherapy provokes selective, TBK1-IRF3 driven innate inflammation that is associated with sustained type-I/III interferon (IFN) release. Despite priming equivalent antitumor T cell quantities, MDA5-orchestrated TBK1-IRF3 signaling, but not NFκB-polarized TLR activation, culminates in polyfunctional and Th1-differentiated antitumor T cell phenotypes. Recombinant type-I IFN increases tumor-localized T cell function, but does not mediate durable antitumor immunotherapy without concomitant pattern recognition receptor (PRR) signaling. Thus, virus-induced MDA5-TBK1-IRF3 signaling in the TME provides PRR-contextualized IFN responses that elicit functional antitumor T cell immunity. TBK1-IRF3 innate signal transduction stimulates eventual function and differentiation of tumor-infiltrating T cells.
Authors
Brown, MC; Mosaheb, MM; Mohme, M; McKay, ZP; Holl, EK; Kastan, JP; Yang, Y; Beasley, GM; Hwang, ES; Ashley, DM; Bigner, DD; Nair, SK; Gromeier, M
MLA Citation
Brown, Michael C., et al. “Viral infection of cells within the tumor microenvironment mediates antitumor immunotherapy via selective TBK1-IRF3 signaling.Nat Commun, vol. 12, no. 1, Mar. 2021, p. 1858. Pubmed, doi:10.1038/s41467-021-22088-1.
URI
https://scholars.duke.edu/individual/pub1477406
PMID
33767151
Source
pubmed
Published In
Nature Communications
Volume
12
Published Date
Start Page
1858
DOI
10.1038/s41467-021-22088-1

Dissecting the immune landscape of tumor draining lymph nodes in melanoma with high-plex spatially resolved protein detection.

BACKGROUND: In melanoma patients, microscopic tumor in the sentinel lymph-node biopsy (SLN) increases the risk of distant metastases, but the transition from tumor in the SLN to metastatic disease remains poorly understood. METHODS: Fluorescent staining for CD3, CD20, CD11c, and DNA was performed on SLN tissue and matching primary tumors. Regions of interest (ROI) were then chosen geometrically (e.g., tumor) or by fluorescent cell subset markers (e.g., CD11c). Each ROI was further analyzed using NanoString Digital Spatial Profiling high-resolution multiplex profiling. Digital counts for 59-panel immune-related proteins were collected and normalized to account for system variation and ROI area. RESULTS: Tumor regions of SLNs had variable infiltration of CD3 cells among patients. The patient with overall survival (OS) > 8 years had the most CD11c- and CD3-expressing cells infiltrating the SLN tumor region. All patients had CD11c (dendritic cell, DC) infiltration into the SLN tumor region. Selecting ROI by specific cell subtype, we compared protein expression of CD11c cells between tumor and non-tumor/normal tissue SLN regions. Known markers of DC activation such as CD86, HLA-DR, and OX40L were lowest on CD11c cells within SLN tumor for the patient with OS < 1 year and highest on the patient with OS > 8 years. CONCLUSION: We demonstrate the feasibility of profiling the protein expression of CD11c cells within the SLN tumor. Identifying early regulators of melanoma control when the disease is microscopically detected in the SLN is beneficial and requires follow-up studies in a larger cohort of patients.
Authors
Beasley, GM; Therien, AD; Holl, EK; Al-Rohil, R; Selim, MA; Farrow, NE; Pan, L; Haynes, P; Liang, Y; Tyler, DS; Hanks, BA; Nair, SK
MLA Citation
Beasley, Georgia M., et al. “Dissecting the immune landscape of tumor draining lymph nodes in melanoma with high-plex spatially resolved protein detection.Cancer Immunol Immunother, vol. 70, no. 2, Feb. 2021, pp. 475–83. Pubmed, doi:10.1007/s00262-020-02698-2.
URI
https://scholars.duke.edu/individual/pub1456222
PMID
32814992
Source
pubmed
Published In
Cancer Immunol Immunother
Volume
70
Published Date
Start Page
475
End Page
483
DOI
10.1007/s00262-020-02698-2

Immune Expression in Children With Vesicoureteral Reflux: A Pilot Study.

OBJECTIVE: To perform an exploratory, descriptive pilot study of the systemic and local immune environment in patients with vesicoureteral reflux (VUR) and bladder-bowel dysfunction (BBD). METHODS: Consecutive children with VUR undergoing intravesical ureteral reimplantation were enrolled. Patients were assessed for presence of BBD by reported patient history and validated questionnaire. Fresh blood and bladder tissue, collected at the time of surgery, were immediately processed for analysis. Immune cell compositions were determined via flow cytometry. Immune cell activation was also defined at the time of analysis. LegendPlex assay analysis was utilized to define levels of circulating chemokines and cytokines. RESULTS: A total of 7 patients were enrolled. Although percentages of circulating immune cells in the blood of those with VUR/BBD and VUR alone were similar, within bladder tissue, VUR/BBD demonstrated increased immune infiltrates compared to VUR alone. Bladder sample analysis showed that B cells, and Effector Memory and Naïve T cell percentages were significantly increased in VUR/BBD patients compared to VUR patients. T cell expression of PD1 was increased in bladder tissues of BBD/VUR. Additionally, analysis of circulating neutrophils displayed significantly increased upregulation of PDL-1 in patients with VUR/BBD vs those with VUR only. CONCLUSION: These pilot data suggest an immune-rich microenvironment is present within VUR. Severity of inflammation appeared to correlate with presence of BBD. This implies that targeting pelvic inflammation may be a novel therapy for children with VUR- or non-VUR-related BBD. Follow-up studies are currently underway.
Authors
Johnston, AW; Routh, JC; Purves, JT; Wiener, JS; Sinani, A; Holl, EK
MLA Citation
Johnston, Ashley W., et al. “Immune Expression in Children With Vesicoureteral Reflux: A Pilot Study.Urology, vol. 148, Feb. 2021, pp. 254–59. Pubmed, doi:10.1016/j.urology.2020.10.003.
URI
https://scholars.duke.edu/individual/pub1462495
PMID
33049235
Source
pubmed
Published In
Urology
Volume
148
Published Date
Start Page
254
End Page
259
DOI
10.1016/j.urology.2020.10.003