Keri M. Sullivan
A5076969910- Immune cells in cancer
- Cancer Immunotherapy and Biomarkers
- Histone Deacetylase Inhibitors Research
- S100 Proteins and Annexins
- Macrophage Migration Inhibitory Factor
- Gastrointestinal motility and disorders
- Pancreatic and Hepatic Oncology Research
- Inflammatory Bowel Disease
- Microscopic Colitis
- Inflammation biomarkers and pathways
- Nanoparticle-Based Drug Delivery
- Inflammatory Biomarkers in Disease Prognosis
- COVID-19 Clinical Research Studies
- Helicobacter pylori-related gastroenterology studies
- T-cell and B-cell Immunology
- Health Systems, Economic Evaluations, Quality of Life
- Immunodeficiency and Autoimmune Disorders
- Colorectal Cancer Treatments and Studies
- SARS-CoV-2 and COVID-19 Research
- Long-Term Effects of COVID-19
- Drug-Induced Adverse Reactions
- Neutropenia and Cancer Infections
- Ethics in Clinical Research
- Economic and Financial Impacts of Cancer
- Pathogenesis and Treatment of Hiccups
Massachusetts General Hospital
2020-2024
Harvard University
2020-2024
New York Hospital Queens
2024
Columbia University
2024
NewYork–Presbyterian Hospital
2024
Marion General Hospital
2018
Abstract Innate inflammation promotes tumor development, although the role of innate inflammatory cytokines in established human tumors is unclear. Herein, we report clinical and translational results from a phase Ib trial testing whether IL1β blockade pancreatic cancer would alleviate myeloid immunosuppression reveal antitumor T-cell responses to PD1 blockade. Patients with treatment-naïve advanced ductal adenocarcinoma (n = 10) were treated canakinumab, high-affinity monoclonal...
Background Recombinant granulocyte colony-stimulating factor (G-CSF) is routinely administered for prophylaxis or treatment of chemotherapy-induced neutropenia. Chronic myelopoiesis and granulopoiesis in patients with cancer has been shown to induce immature monocytes neutrophils that contribute both systemic local immunosuppression the tumor microenvironment. The effect recombinant G-CSF (pegfilgrastim filgrastim) on production myeloid-derived suppressive cells unknown. Here we examined...
The paper has been withdrawn owing to erroneous inclusion of confidential information relating a third party.
Immune-related adverse events (irAE) secondary to immune checkpoint inhibitors (ICI) have gastrointestinal (GI) manifestations, including gastritis, enteritis, and/or colitis. The long-term sequelae of ICI-associated GI toxicities (GI-irAE), particularly the development disorders gut-brain interaction, are not well known. We characterized incidence persistent symptoms after GI-irAE.
<div>Abstract<p>Innate inflammation promotes tumor development, although the role of innate inflammatory cytokines in established human tumors is unclear. Herein, we report clinical and translational results from a phase Ib trial testing whether IL1β blockade pancreatic cancer would alleviate myeloid immunosuppression reveal antitumor T-cell responses to PD1 blockade. Patients with treatment-naïve advanced ductal adenocarcinoma (<i>n</i> = 10) were treated...
<p>Supplemental Table 1: Selected Adverse Events reported in ≥5 subjects (any grade) or ≥3 for Grade 3 from patients SR-1. Select immune-related adverse events are also shown.</p>
<p>Supplemental Table 3: Serum samples from baseline and on-treatment time points patients in SR-1, the standard of care cohort, healthy people who donated blood 28 days apart were analyzed by cytokine bead array. Significance was determined Wilcoxon matched-pairs signed rank test.</p>
<p>Supplemental Figure 4: Flow cytometry gating strategy for the PBMC samples shown in Figures 2 and 3.</p>
<p>Supplemental Figure 5: Addition of TNFa ameliorates myeloid suppression in vitro. (A) Histogram HLA-DR mean fluorescence intensity CD33<sup>+</sup> SSCA high cells from monocytes cocultured for a week with 75 pg/ML M-CSF the addition 10 ng/mL each GM-CSF/ IL-6 or 10ng/mL IL-1b without an blocking antibody. (B) Induced MoMDSCs panel A were then cultured CFSE-labeled T 3 days coculture at 1:1 ratio, and cell proliferation was assessed by flow cytometry. Proliferation...
<p>Supplemental Figure 4: Flow cytometry gating strategy for the PBMC samples shown in Figures 2 and 3.</p>
<p>Supplemental Figure 2: Pharmacokinetics of canakinumab. Serum levels canakinumab were measured in patients on SR-1 at the indicated time points.</p>
<p>Supplemental Figure 6. Cell populations identified by transcriptional profiling from tumor biopsies. (A) UMAP of all cells in the dataset, colored cluster. (B-C) Relative expression representative genes six major compartments across full dataset. (D) IL1B, IL1R1, PDCD1, PDCDLG1, and PDCDLG2 (E) The percent each myeloid cluster that is found samples, separated into baseline treated subgroups (Wilcoxon rank-sum test).</p>
<p>Supplemental Figure 3: Presence of canakinumab does not interfere with the ability to detect IL-1b in patient serum. Baseline serum from three randomly selected patients pancreatic ductal adenocarcinoma was evaluated by cytokine bead array for IL-1b. For each sample, spiked at indicated concentrations. Note that measured values were consistent across all samples same patient, regardless presence canakinumab.</p>
<p>Supplemental Figure 7: Macrophage subtypes are unaffected by treatment in patients SR-1. (A) Baseline and on-treatment biopsies from (<i>n</i> = 6 paired samples) the SR-1 trial were analyzed multiplex immunofluorescence using indicated antibodies. Representative image of macrophage panel is shown. (B) Densities total macrophages (CD68<sup>+</sup> or CD163<sup>+</sup> cells). (C) M1 polarized...
<p>Supplemental Figure 6. Cell populations identified by transcriptional profiling from tumor biopsies. (A) UMAP of all cells in the dataset, colored cluster. (B-C) Relative expression representative genes six major compartments across full dataset. (D) IL1B, IL1R1, PDCD1, PDCDLG1, and PDCDLG2 (E) The percent each myeloid cluster that is found samples, separated into baseline treated subgroups (Wilcoxon rank-sum test).</p>
<p>Supplemental Figure 1: Progression-free survival for SR-1, an open-label multicenter phase Ib study evaluating gemcitabine, n(ab)-paclitaxel, canakinumab and spartalizumab in advanced pancreatic ductal adenocarcinoma. A) PFS the 10 patients SR-1 is shown. B) OS C) 11 GnP cohort shown.</p>
<p>Supplemental Figure 2: Pharmacokinetics of canakinumab. Serum levels canakinumab were measured in patients on SR-1 at the indicated time points.</p>
<p>Supplemental Table 2: Patient sample information and types of experimental data collected from each patient.</p>
<p>Supplemental Table 3: Serum samples from baseline and on-treatment time points patients in SR-1, the standard of care cohort, healthy people who donated blood 28 days apart were analyzed by cytokine bead array. Significance was determined Wilcoxon matched-pairs signed rank test.</p>
<p>Supplemental Table 2: Patient sample information and types of experimental data collected from each patient.</p>
<p>Supplemental Table 1: Selected Adverse Events reported in ≥5 subjects (any grade) or ≥3 for Grade 3 from patients SR-1. Select immune-related adverse events are also shown.</p>