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Eda K Holl

Adjunct Assistant Professor in the Department of Surgery
Surgery, Surgical Sciences

Selected Publications


Functional reprogramming of peripheral blood monocytes by soluble mediators in patients with pancreatic cancer and intraductal papillary mucinous neoplasms.

Journal Article Front Immunol · 2023 BACKGROUND: Monocytes and monocyte-derived tumor infiltrating cells have been implicated in the immunosuppression and immune evasion associated with pancreatic adenocarcinoma (PDAC). Yet, precisely how monocytes in the periphery and tumor microenvironment ... Full text Link to item Cite

Multimodality analysis confers a prognostic benefit of a T-cell infiltrated tumor microenvironment and peripheral immune status in patients with melanoma.

Journal Article J Immunother Cancer · September 2022 BACKGROUND: We previously reported results from a phase 1 study testing intratumoral recombinant poliovirus, lerapolturev, in 12 melanoma patients. All 12 patients received anti-PD-1 systemic therapy before lerapolturev, and 11 of these 12 patients also re ... Full text Link to item Cite

Spatial biology analysis reveals B cell follicles in secondary lymphoid structures may regulate anti-tumor responses at initial melanoma diagnosis.

Journal Article Front Immunol · 2022 INTRODUCTION: B cells are key regulators of immune responses in melanoma. We aimed to explore differences in the histologic location and activation status of B cell follicles in sentinel lymph nodes (SLN) of melanoma patients. METHODS: Flow cytometry was p ... Full text Link to item Cite

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

Journal Article Ann Surg Oncol · July 2021 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, ... Full text Link to item Cite

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

Journal Article Mol Ther · May 5, 2021 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 ... Full text Link to item Cite

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

Journal Article Nat Commun · March 25, 2021 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 antit ... Full text Link to item Cite

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

Journal Article Cancer Immunol Immunother · February 2021 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 fo ... Full text Link to item Cite

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

Journal Article Urology · February 2021 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 uret ... Full text Link to item Cite

Prolonged PSA stabilization and overall survival following sipuleucel-T monotherapy in metastatic castration-resistant prostate cancer patients.

Journal Article Prostate Cancer Prostatic Dis · December 2019 BACKGROUND: Sipuleucel-T is an autologous cellular immunotherapy that is FDA approved for the treatment of asymptomatic or minimally symptomatic metastatic castrate-resistant prostate cancer (mCRPC). The IMPACT registry trial demonstrated a 4.1 month survi ... Full text Link to item Cite

Immune expression in children with Wilms tumor: a pilot study.

Journal Article J Pediatr Urol · October 2019 BACKGROUND: Given improvements in multimodality therapy, survival among children with Wilms tumor (WT) exceeds 90%. However, 15% of children with favorable histology and 50% of children with anaplastic WT experience recurrence or progression. Of patients w ... Full text Link to item Cite

Examining Peripheral and Tumor Cellular Immunome in Patients With Cancer.

Journal Article Front Immunol · 2019 Immunotherapies are rapidly being integrated into standard of care (SOC) therapy in conjunction with surgery, chemotherapy, and radiotherapy for many cancers and a large number of clinical studies continue to explore immunotherapy alone and as part of comb ... Full text Link to item Cite

Cancer immunotherapy with recombinant poliovirus induces IFN-dominant activation of dendritic cells and tumor antigen-specific CTLs.

Journal Article Sci Transl Med · September 20, 2017 Tumors thrive in an immunosuppressive microenvironment that impedes antitumor innate and adaptive immune responses. Thus, approaches that can overcome immunosuppression and engage antitumor immunity are needed. This study defines the adjuvant and cancer im ... Full text Link to item Cite

Recombinant oncolytic poliovirus, PVSRIPO, has potent cytotoxic and innate inflammatory effects, mediating therapy in human breast and prostate cancer xenograft models.

Journal Article Oncotarget · November 29, 2016 Intratumoral inoculation of viruses with tumor-selective cytotoxicity may induce cancer cell death and, thereby, shrink neoplastic lesions. It is unlikely, however, that viral tumor cell killing alone could produce meaningful, durable clinical responses, a ... Full text Link to item Cite

Erratum: Scavenging nucleic acid debris to combat autoimmunity and infectious disease (Proceedings of the National Academy of Sciences of the United States of America (2016) 113: 35 (9728-9733) DOI: 10.1073/pnas.1607011113)

Journal Article Proceedings of the National Academy of Sciences of the United States of America · October 18, 2016 ENGINEERING: Correction for "Scavenging nucleic acid debris to combat autoimmunity and infectious disease," by Eda K. Holl, Kara L. Shumansky, Luke B. Borst, Angela D. Burnette, Christopher J. Sample, Elizabeth A. Ramsburg, and Bruce A. Sullenger, which ap ... Full text Cite

Scavenging nucleic acid debris to combat autoimmunity and infectious disease.

Journal Article Proc Natl Acad Sci U S A · August 30, 2016 Nucleic acid-containing debris released from dead and dying cells can be recognized as damage-associated molecular patterns (DAMPs) or pattern-associated molecular patterns (PAMPs) by the innate immune system. Inappropriate activation of the innate immune ... Full text Link to item Cite

RNA-Based Vaccines in Cancer Immunotherapy.

Journal Article J Immunol Res · 2015 RNA vaccines traditionally consist of messenger RNA synthesized by in vitro transcription using a bacteriophage RNA polymerase and template DNA that encodes the antigen(s) of interest. Once administered and internalized by host cells, the mRNA transcripts ... Full text Open Access Link to item Cite

The nucleic acid scavenger polyamidoamine third-generation dendrimer inhibits fibroblast activation and granulation tissue contraction.

Journal Article Plast Reconstr Surg · September 2014 BACKGROUND: Pathologic cutaneous scarring affects over 40 million people worldwide and costs billions of dollars annually. Understanding mechanisms of fibroblast activation and granulation tissue contraction is the first step toward preventing pathologic s ... Full text Link to item Cite

Immune plexins and semaphorins: old proteins, new immune functions.

Journal Article Protein Cell · January 2013 Plexins and semaphorins are a large family of proteins that are involved in cell movement and response. The importance of plexins and semaphorins has been emphasized by their discovery in many organ systems including the nervous (Nkyimbeng-Takwi and Chapov ... Full text Link to item Cite

Generation of bone marrow and fetal liver chimeric mice.

Journal Article Methods Mol Biol · 2013 The creation of bone marrow and fetal liver chimeric mice has proven to be a valuable tool in the field of immunology. Chimeric mice are used to study the contribution of various cell types of hematopoietic versus non-hematopoietic origin in the course of ... Full text Link to item Cite

Functional reprogramming of peripheral blood monocytes by soluble mediators in patients with pancreatic cancer and intraductal papillary mucinous neoplasms.

Journal Article Front Immunol · 2023 BACKGROUND: Monocytes and monocyte-derived tumor infiltrating cells have been implicated in the immunosuppression and immune evasion associated with pancreatic adenocarcinoma (PDAC). Yet, precisely how monocytes in the periphery and tumor microenvironment ... Full text Link to item Cite

Multimodality analysis confers a prognostic benefit of a T-cell infiltrated tumor microenvironment and peripheral immune status in patients with melanoma.

Journal Article J Immunother Cancer · September 2022 BACKGROUND: We previously reported results from a phase 1 study testing intratumoral recombinant poliovirus, lerapolturev, in 12 melanoma patients. All 12 patients received anti-PD-1 systemic therapy before lerapolturev, and 11 of these 12 patients also re ... Full text Link to item Cite

Spatial biology analysis reveals B cell follicles in secondary lymphoid structures may regulate anti-tumor responses at initial melanoma diagnosis.

Journal Article Front Immunol · 2022 INTRODUCTION: B cells are key regulators of immune responses in melanoma. We aimed to explore differences in the histologic location and activation status of B cell follicles in sentinel lymph nodes (SLN) of melanoma patients. METHODS: Flow cytometry was p ... Full text Link to item Cite

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

Journal Article Ann Surg Oncol · July 2021 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, ... Full text Link to item Cite

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

Journal Article Mol Ther · May 5, 2021 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 ... Full text Link to item Cite

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

Journal Article Nat Commun · March 25, 2021 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 antit ... Full text Link to item Cite

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

Journal Article Cancer Immunol Immunother · February 2021 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 fo ... Full text Link to item Cite

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

Journal Article Urology · February 2021 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 uret ... Full text Link to item Cite

Prolonged PSA stabilization and overall survival following sipuleucel-T monotherapy in metastatic castration-resistant prostate cancer patients.

Journal Article Prostate Cancer Prostatic Dis · December 2019 BACKGROUND: Sipuleucel-T is an autologous cellular immunotherapy that is FDA approved for the treatment of asymptomatic or minimally symptomatic metastatic castrate-resistant prostate cancer (mCRPC). The IMPACT registry trial demonstrated a 4.1 month survi ... Full text Link to item Cite

Immune expression in children with Wilms tumor: a pilot study.

Journal Article J Pediatr Urol · October 2019 BACKGROUND: Given improvements in multimodality therapy, survival among children with Wilms tumor (WT) exceeds 90%. However, 15% of children with favorable histology and 50% of children with anaplastic WT experience recurrence or progression. Of patients w ... Full text Link to item Cite

Examining Peripheral and Tumor Cellular Immunome in Patients With Cancer.

Journal Article Front Immunol · 2019 Immunotherapies are rapidly being integrated into standard of care (SOC) therapy in conjunction with surgery, chemotherapy, and radiotherapy for many cancers and a large number of clinical studies continue to explore immunotherapy alone and as part of comb ... Full text Link to item Cite

Cancer immunotherapy with recombinant poliovirus induces IFN-dominant activation of dendritic cells and tumor antigen-specific CTLs.

Journal Article Sci Transl Med · September 20, 2017 Tumors thrive in an immunosuppressive microenvironment that impedes antitumor innate and adaptive immune responses. Thus, approaches that can overcome immunosuppression and engage antitumor immunity are needed. This study defines the adjuvant and cancer im ... Full text Link to item Cite

Recombinant oncolytic poliovirus, PVSRIPO, has potent cytotoxic and innate inflammatory effects, mediating therapy in human breast and prostate cancer xenograft models.

Journal Article Oncotarget · November 29, 2016 Intratumoral inoculation of viruses with tumor-selective cytotoxicity may induce cancer cell death and, thereby, shrink neoplastic lesions. It is unlikely, however, that viral tumor cell killing alone could produce meaningful, durable clinical responses, a ... Full text Link to item Cite

Erratum: Scavenging nucleic acid debris to combat autoimmunity and infectious disease (Proceedings of the National Academy of Sciences of the United States of America (2016) 113: 35 (9728-9733) DOI: 10.1073/pnas.1607011113)

Journal Article Proceedings of the National Academy of Sciences of the United States of America · October 18, 2016 ENGINEERING: Correction for "Scavenging nucleic acid debris to combat autoimmunity and infectious disease," by Eda K. Holl, Kara L. Shumansky, Luke B. Borst, Angela D. Burnette, Christopher J. Sample, Elizabeth A. Ramsburg, and Bruce A. Sullenger, which ap ... Full text Cite

Scavenging nucleic acid debris to combat autoimmunity and infectious disease.

Journal Article Proc Natl Acad Sci U S A · August 30, 2016 Nucleic acid-containing debris released from dead and dying cells can be recognized as damage-associated molecular patterns (DAMPs) or pattern-associated molecular patterns (PAMPs) by the innate immune system. Inappropriate activation of the innate immune ... Full text Link to item Cite

RNA-Based Vaccines in Cancer Immunotherapy.

Journal Article J Immunol Res · 2015 RNA vaccines traditionally consist of messenger RNA synthesized by in vitro transcription using a bacteriophage RNA polymerase and template DNA that encodes the antigen(s) of interest. Once administered and internalized by host cells, the mRNA transcripts ... Full text Open Access Link to item Cite

The nucleic acid scavenger polyamidoamine third-generation dendrimer inhibits fibroblast activation and granulation tissue contraction.

Journal Article Plast Reconstr Surg · September 2014 BACKGROUND: Pathologic cutaneous scarring affects over 40 million people worldwide and costs billions of dollars annually. Understanding mechanisms of fibroblast activation and granulation tissue contraction is the first step toward preventing pathologic s ... Full text Link to item Cite

Immune plexins and semaphorins: old proteins, new immune functions.

Journal Article Protein Cell · January 2013 Plexins and semaphorins are a large family of proteins that are involved in cell movement and response. The importance of plexins and semaphorins has been emphasized by their discovery in many organ systems including the nervous (Nkyimbeng-Takwi and Chapov ... Full text Link to item Cite

Generation of bone marrow and fetal liver chimeric mice.

Journal Article Methods Mol Biol · 2013 The creation of bone marrow and fetal liver chimeric mice has proven to be a valuable tool in the field of immunology. Chimeric mice are used to study the contribution of various cell types of hematopoietic versus non-hematopoietic origin in the course of ... Full text Link to item Cite

Nucleic acid scavenging polymers inhibit extracellular DNA-mediated innate immune activation without inhibiting anti-viral responses.

Journal Article PLoS One · 2013 Toll-like receptor (TLR) family members, 3, 7 and 9 are key components in initiation and progression of autoimmune disorders such as systemic lupus erythematosus (SLE). These TLRs are often referred to as nucleic acid-sensing TLRs based on their ability to ... Full text Link to item Cite

The innate immune sensor NLRC3 attenuates Toll-like receptor signaling via modification of the signaling adaptor TRAF6 and transcription factor NF-κB.

Journal Article Nat Immunol · September 2012 Several members of the NLR family of sensors activate innate immunity. In contrast, we found here that NLRC3 inhibited Toll-like receptor (TLR)-dependent activation of the transcription factor NF-κB by interacting with the TLR signaling adaptor TRAF6 to at ... Full text Link to item Cite

Nucleic acid scavengers inhibit thrombosis without increasing bleeding.

Journal Article Proc Natl Acad Sci U S A · August 7, 2012 Development of effective, yet safe, antithrombotic agents has been challenging because such agents increase the propensity of patients to bleed. Recently, naturally occurring polyphosphates such as extracellular DNA, RNA, and inorganic polyphosphates have ... Full text Link to item Cite

Plexin-B2 and Plexin-D1 in dendritic cells: expression and IL-12/IL-23p40 production.

Journal Article PLoS One · 2012 Plexins are a family of genes (A,B,C, and D) that are expressed in many organ systems. Plexins expressed in the immune system have been implicated in cell movement and cell-cell interaction during the course of an immune response. In this study, the expres ... Full text Link to item Cite

Plexin-D1 is a novel regulator of germinal centers and humoral immune responses.

Journal Article J Immunol · May 15, 2011 Long-lived humoral immune responses depend upon the generation of memory B cells and long-lived plasma cells during the germinal center (GC) reaction. These memory compartments, characterized by class-switched IgG and high-affinity Abs, are the basis for s ... Full text Link to item Cite

Plexin-B2 negatively regulates macrophage motility, Rac, and Cdc42 activation.

Journal Article PLoS One · 2011 Plexins are cell surface receptors widely studied in the nervous system, where they mediate migration and morphogenesis though the Rho family of small GTPases. More recently, plexins have been implicated in immune processes including cell-cell interaction, ... Full text Link to item Cite

The NLRP3 inflammasome functions as a negative regulator of tumorigenesis during colitis-associated cancer.

Journal Article J Exp Med · May 10, 2010 Colitis-associated cancer (CAC) is a major complication of inflammatory bowel diseases. We show that components of the inflammasome are protective during acute and recurring colitis and CAC in the dextran sulfate sodium (DSS) and azoxymethane + DSS models. ... Full text Link to item Cite

The NLRP3 inflammasome mediates in vivo innate immunity to influenza A virus through recognition of viral RNA.

Journal Article Immunity · April 17, 2009 The nucleotide-binding domain and leucine-rich-repeat-containing (NLR) family of pattern-recognition molecules mediate host immunity to various pathogenic stimuli. However, in vivo evidence for the involvement of NLR proteins in viral sensing has not been ... Full text Link to item Cite

Semaphorin 6D regulates the late phase of CD4+ T cell primary immune responses.

Journal Article Proc Natl Acad Sci U S A · September 2, 2008 The semaphorin and plexin family of ligand and receptor proteins provides important axon guidance cues required for development. Recent studies have expanded the role of semaphorins and plexins in the regulation of cardiac, circulatory and immune system fu ... Full text Link to item Cite