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PRJNA1107274 SRP505422

Gut microbiome in melanoma patients on vidutolimod plus nivolumab

Neoadjuvant Vidutolimod and Nivolumab in High-Risk Resectable Melanoma

113 gut microbiome samples from adult and elderly melanoma patients in Pittsburgh, USA, from a single-arm phase 2 neoadjuvant trial of TLR9 agonist vidutolimod combined with anti-PD-1 nivolumab. machine-written summary

113 samples · 113 runs · US · Age unknown · 2024 · 7.24 Gbp / sample

Sources
✓Sequence archive 1,356○Abstract / description✓Full text 226–Supplementary tables–External resources–User contribution–Human verified

Checked this project's papers and archive records yourself? Mark it human-verified.

what each source gave
✓ Sequence archive1,356 sample values (age, collection date, country, intervention, intervention detail, latitude, location locality, location region)
○ Abstract / descriptionread; no usable statement
✓ Full text226 sample values (health condition, health condition detail) · PMC11560503
– Supplementary tablesno supplementary tables available (or none open access)
– External resourcesnot covered by the external resources we ingest
– User contributionnothing uploaded yet
– Human verifiednot yet checked by a person · I checked this project — verify it
Interventions

intervention · arms resolved

before · no interventionbefore · no interventi26 samplesdrugdrug87 samples
single arm: samples before and on the intervention

25 people have samples in more than one arm.

Non-antibiotic pharmaceutical given as the study intervention (metformin design single_arm_before_after · population other_cancer · Neoadjuvant TLR9 agonist vidutolimod plus anti-PD-1 nivolumab

“neoadjuvant TLR9 agonist vidutolimod combined with anti-PD-1 nivolumab” — abstract:39486411 (study level; per-sample arms are in the intervention column below)

Samples at a glance
1 sampling locations · 1 country
Age
adult65
elderly48
Condition
other_cancer113
Sex
male68
female45
Country
US113
Body site
primary113
Collected 2018–2021
2018: 6 samples2019: 73 samples2020: 31 samples2021: 3 samples20182021
Sequencing depth per sample · this project all projects
all projects, 0–0.03 Gbp: 25,080 samples (4 %)all projects, 0.03–0.1 Gbp: 17,066 samples (3 %)all projects, 0.1–0.3 Gbp: 29,179 samples (5 %)all projects, 0.3–1 Gbp: 47,044 samples (8 %)all projects, 1–3 Gbp: 124,983 samples (22 %)this project, 1–3 Gbp: 11 samplesall projects, 3–10 Gbp: 253,728 samples (44 %)this project, 3–10 Gbp: 78 samplesall projects, 10–30 Gbp: 72,533 samples (13 %)this project, 10–30 Gbp: 24 samplesall projects, 30–100 Gbp: 3,024 samples (1 %)all projects, 100–300 Gbp: 106 samples (0 %)all projects, ≥ 300 Gbp: 9 samples (0 %)project median 7.24 Gbp per sample0130Gbp
Sampling design and relatedness

longitudinal

27 of 30 people sampled more than once (110 samples; median 4, up to 5 per person) · follow-up median 11 mo (max 18 mo) · median interval between samples 2 mo (time from collection months (month precision)). Schedule stated by the source: “Repeated fecal sampling per subject across neoadjuvant treatment and follow-up, binned at stated timepoint_days_bin values (1,14,42,63,84,112, etc.), with intermediate timepoints flagged.”.

UOP-004UOP-004: day 0UOP-004: day 30UOP-004: day 30UOP-004: day 151UOP-004: day 365UOP-005UOP-005: day 0UOP-005: day 59UOP-005: day 365UOP-007UOP-007: day 0UOP-007: day 31UOP-007: day 31UOP-007: day 90UOP-007: day 334UOP-008UOP-008: day 0UOP-008: day 0UOP-008: day 28UOP-008: day 120UOP-008: day 212UOP-010UOP-010: day 0UOP-010: day 28UOP-010: day 28UOP-010: day 150UOP-010: day 425UOP-011UOP-011: day 0UOP-011: day 31UOP-011: day 92UOP-011: day 427UOP-012UOP-012: day 0UOP-012: day 31UOP-012: day 92UOP-013UOP-013: day 0UOP-013: day 61UOP-013: day 184UOP-014UOP-014: day 0UOP-014: day 31UOP-014: day 61UOP-014: day 122UOP-014: day 397UOP-015UOP-015: day 0UOP-015: day 31UOP-015: day 31UOP-015: day 122UOP-015: day 550UOP-016UOP-016: day 0UOP-016: day 0UOP-016: day 30UOP-016: day 91UOP-016: day 244UOP-018UOP-018: day 0UOP-018: day 0UOP-018: day 61UOP-018: day 92UOP-018: day 550UOP-019UOP-019: day 0UOP-019: day 31UOP-019: day 61UOP-019: day 153UOP-019: day 397UOP-021UOP-021: day 0UOP-021: day 30UOP-021: day 61UOP-021: day 122UOP-022UOP-022: day 0UOP-022: day 0UOP-022: day 31UOP-022: day 92UOP-023UOP-023: day 0UOP-023: day 31UOP-024UOP-024: day 0UOP-024: day 31UOP-024: day 31UOP-024: day 123UOP-024: day 336UOP-025UOP-025: day 0UOP-025: day 31UOP-025: day 62UOP-026UOP-026: day 0UOP-026: day 31UOP-026: day 61UOP-027UOP-027: day 0UOP-027: day 31UOP-027: day 61UOP-027: day 123UOP-027: day 336UOP-030UOP-030: day 0UOP-030: day 61UOP-030: day 121UOP-030: day 486UOP-032UOP-032: day 0UOP-032: day 0UOP-032: day 29UOP-033UOP-033: day 0UOP-033: day 0UOP-033: day 31UOP-033: day 122UOP-034UOP-034: day 0UOP-034: day 30UOP-034: day 122UOP-035UOP-035: day 0UOP-035: day 0UOP-035: day 30UOP-035: day 30UOP-035: day 426UOP-036UOP-036: day 0UOP-036: day 31UOP-036: day 61UOP-036: day 61UOP-036: day 3350 d5 mo9 mo14 mo18 mo

Each row is one person (26 shown of 27); dots are samples at days since that person's first sample.

How longitudinal and relatedness information is derived

Community composition
Blautia_A 13.0%Roseburia 5.9%Bacteroides 5.4%Faecalibacterium 4.5%Bifidobacterium 4.3%Collinsella 3.6%Streptococcus 3.6%Mediterraneibacter 3.3%Ruminococcoides 3.3%Phocaeicola 3.2%Fusicatenibacter 2.5%Gemmiger 2.2%not assigned to a genus 4.0%other genera 41.2%

Genera, mean relative abundance over 106 profiled gut samples of this project (Sandpiper SingleM profiles, GTDB R232; low-depth and non-metagenome profiles left out).

Field coverage
fieldsamplescoverageR1R2R3R4
age_category113 100%
country113 100%113
health_condition113 100%113
subject_id113 100%113
age_at_collection_days113 100%113
collection_date113 100%113
detailed_location113 100%
health_condition_detail113 100%113
intervention113 100%113
intervention_detail113 100%113
latitude113 100%113
location_locality113 100%113
location_region113 100%113
longitude113 100%113
sex113 100%113
timepoint_label113 100%113
Papers (1)
  • Neoadjuvant vidutolimod and nivolumab in high-risk resectable melanoma: A prospective phase II trial. 2024 PMID 39486411 PMC11560503 unsure
Details
Archive description

Intratumoral TLR9 agonists and anti-PD-1 therapies provide durable clinical responses and broad immune activation. To evaluate the efficacy and mechanisms of action of this therapeutic combination, we conducted a single-arm phase 2 neoadjuvant study of TLR9 agonist vidutolimod combined with anti-PD-1 nivolumab in patients with high-risk resectable melanoma. In 31 evaluable patients, 55% (17/31) had major pathologic response (MPR), with eight grade 3 treatment-related adverse events. MPR was associated with necrosis, and melanophagocytosis with increased CD8+ tumor-infiltrating lymphocytes and plasmacytoid dendritic cells (pDCs) in the tumor microenvironment, and increased frequencies of Ki67+ CD8+ and CD4+ T cells, pDCs, and monocytes peripherally. Patients with MPR had an enriched pre-treatment gene signature of myeloid cells , and response to therapy was associated with gene signatures of immune cells, pDCs, phagocytosis, and macrophage activation. Patients with MPR also had gut microbial signatures enriched for Gram-negative bacteria belonging to the Bacteroidaceae and Enterobacteriaceae families and the small subgroup of Gram-negative Firmicutes. Our findings support that combined vidutolimod and nivolumab stimulates a broad antitumor immune response and is associated with distinct baseline myeloid gene signature and gut microbiome composition.

How this project entered the registry

Classified as human gut / stool shotgun DNA metagenome of adult and elderly by opus_adjudicated with confidence 0.80. Assay shotgun_dna.

  • host run.host_tax_id · “9606”
  • host study.description · “patients with high-risk resectable melanoma”
  • body site study.description · “gut microbial signatures enriched for Gram-negative bacteria”
  • life stage sample.attr.age · “58 (n=56/113)”
  • life stage sample.attr.age · “66 (n=54/113)”
Evidence examples (one per field × route)
samplefieldvaluerouteconf.sourcequote
SAMN41879536age_at_collection_days21915.0R10.85sample.attr.age60
SAMN41879536collection_date2018-11R10.90biosample.attribute:collection_date2018-11
SAMN41879536countryUSR10.90sample.attr.geo_loc_nameUSA: Pittsburgh
SAMN41879536health_conditionother_cancerR30.70paper.fulltext.methodsclinical stage III cutaneous melanoma according to the American Joint Committee
SAMN41879536health_condition_detailhigh-risk resectable stage III cutaneous melanomaR30.70paper.fulltext.methodsclinical stage III cutaneous melanoma according to the American Joint Committee
SAMN41879536interventionno_interventionR10.80biosample.attribute:Timepoint_days_binTimepoint_days_bin: 1
SAMN41879536intervention_detailTimepoint_days_bin = 1 (before intervention start)R10.80biosample.attribute:Timepoint_days_binTimepoint_days_bin: 1
SAMN41879536latitude40.4540R10.90biosample.attribute:lat_lon40.454 N 79.933 W
SAMN41879536location_localityPittsburghR10.85biosample.attribute:geo_loc_nameUSA: Pittsburgh
SAMN41879536location_regionPennsylvaniaR10.60biosample.attribute:lat_lon40.454 N 79.933 W
SAMN41879536longitude-79.9330R10.90biosample.attribute:lat_lon40.454 N 79.933 W
SAMN41879536sexmaleR10.90sample.attr.gendermale
SAMN41879536subject_idUOP-004R10.85sample.attr.patient_idUOP-004
SAMN41879536timepoint_label1R10.85biosample.attribute:timepoint_days_bin1
Sequencing

113 runs over 113 samples · mean 7.26 Gbp per run (median 7.24 Gbp, total 820.88 Gbp; 113 runs with a base count) · layout PAIRED 113 · platform ILLUMINA 113 · models Illumina NovaSeq 6000 (113) · 94% of runs with a Sandpiper profile · first public 2024-09-27

Authors (53)

Davar D first · Morrison RM · Dzutsev AK · Karunamurthy A · Chauvin JM · Amatore F · Deutsch JS · Das Neves RX · Rodrigues RR · McCulloch JA · Wang H · Hartman DJ · Badger JH · Fernandes MR · Bai Y · Sun J · Cole AM · Aggarwal P · Fang JR · Deitrick C · Bao R · Duvvuri U · Sridharan SS · Kim SW · A Choudry H · Holtzman MP · Pingpank JF · O'Toole JP · DeBlasio R · Jin Y · Ding Q · Gao W · Groetsch C · Pagliano O · Rose A · Urban C · Singh J · Divarkar P · Mauro D · Bobilev D · Wooldridge J · Krieg AM · Fury MG · Whiteaker JR · Zhao L · Paulovich AG · Najjar YG · Luke JJ · Kirkwood JM · Taube JM · Park HJ · Trinchieri G · Zarour HM last

Downloads

PRJNA1107274.csv.gz (5.0 KB) · parquet (77.3 KB) — all 113 samples, every field with route and confidence · PRJNA1107274_determinations.csv.gz (12.6 KB) — 1,582 evidence rows

Samples (113 · every field this project has values for · hover a cell for its source)
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