Evidence map›Paper›PMID 35277457›Full record

ArticleJournal for immunotherapy of cancer2022

The vaccine-site microenvironment: impacts of antigen, adjuvant, and same-site vaccination on antigen presentation and immune signaling.

Max O Meneveau, Pankaj Kumar, Kevin T Lynch, Sapna P Patel, Craig L Slingluff

Open access · goldAbstract read
In one paragraph

Article in Journal for immunotherapy of cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.5field-weighted citation impact, top 18% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 19 citations in OpenAlex.

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  14. Emergence of SARS-CoV-2 spike protein at the vaccination site.Immunity, inflammation and disease · 2023
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 3 institutions in 1 country.

Max O MeneveauDepartment of Surgery, University of Virginia, Charlottesville, Virginia, USA meneveau@virginia.edu.ORCID 0000-0002-8410-061X
Pankaj KumarDepartment of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, Virginia, USA.
Kevin T LynchDepartment of Surgery, University of Virginia, Charlottesville, Virginia, USA.
Sapna P PatelDepartment of Melanoma/Medical Oncology, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.ORCID 0000-0003-1339-1517
Craig L SlingluffDepartment of Surgery, University of Virginia, Charlottesville, Virginia, USA.ORCID 0000-0002-6664-4373
University of Virginia · USThe University of Texas MD Anderson Cancer Center · USUniversity of Virginia Cancer Center

Funding

Women's Oncology Program - WONP30CA044579 · NCI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI Dina Gould Halme · 1987 to 2026
$72.1M
Cardiovascular Surgery Training ProgramT32HL007849 · NHLBI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI KRON, IRVING L., LAUBACH, VICTOR E · 1998 to 2025
$7.0M
Postdoctoral Training Grant for MDs in Surgical Oncology ResearchT32CA163177 · NCI · UNIVERSITY OF VIRGINIA · PI Craig Lee Slingluff, Allan Tsung · 2011 to 2026
$4.6M
MELANOMA VACCINES USING MHC-ASSOCIATED PEPTIDESR01CA057653 · NCI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI SLINGLUFF, CRAIG LEE · 1997 to 2012
$3.4M
MELANOMA VACCINE FOR HELPER T CELLS COMBINED WITH TARGETED OR IMMUNE THERAPIESR01CA178846 · NCI · UNIVERSITY OF VIRGINIA · PI SLINGLUFF, CRAIG LEE · 2015 to 2017
$1.2M
NCI NIH HHS P30 CA044579NCI NIH HHS R01 CA057653NCI NIH HHS R01 CA178846NCI NIH HHS T32 CA163177NHLBI NIH HHS T32 HL007849
6 · The paper itself

Abstract

backgroundA goal of cancer vaccines is to induce strong T cell responses to tumor antigens, but the delivery method, schedule, and formulation of cancer vaccines have not yet been optimized. Adjuvants serve to increase the immune response against vaccine antigens. However, little is known about the impact of adjuvants plus antigen and their delivery schedule on the immunologic milieu in the vaccine-site microenvironment (VSME). We hypothesized that antigen processing and presentation may occur directly in the VSME, that adding the toll-like receptor 3 (TLR3) agonist polyICLC (pICLC) would enhance markers of immune activation, and that the immune signatures would be enhanced further by repeated vaccination in the same skin site rather than after multiple vaccines in different skin locations.

methodsUsing RNA sequencing, we evaluated VSME biopsies from patients undergoing subcutaneous/intradermal peptide vaccination against melanoma, with incomplete Freund's adjuvant (IFA) with or without pICLC. Differential gene expression analyses and gene set enrichment analyses were performed using R. False discovery rate corrected p values <0.05 were considered significant.

resultsWe found that addition of peptide antigens to IFA enhanced antigen presentation pathways and a tertiary lymphoid structure gene-signature locally at the VSME. Addition of pICLC to IFA + peptide induced an immunologically favorable VSME 1 week after injection but had little impact on the VSME after three injections, compared with IFA + peptide alone. Repeated same-site injection of IFA + peptide antigens induced a VSME with more dendritic cell activation, Th1 dominance, and TLR adaptor protein gene expression than that induced by injections at different, rotating skin locations.

conclusionsThese data suggest that the vaccine-site itself may be a critically important location contributing to vaccine immunity rather than just the draining lymph node, that IFA induces a favorable VSME with TLR agonist being most beneficial early in the vaccine course, and that same-site injections lead to persistent stimulation of immune pathways that may be beneficial in eliciting antigen specific T cell expansion.

Indexed as

Cancer VaccinesAdjuvants, ImmunologicAntigen PresentationHumansVaccinationVaccines, SubunitAdjuvants, ImmunologicCancer VaccinesVaccines, Subunitadjuvants, immunologicantigen presentationarginasemelanomavaccination

Identifiers

PMID35277457
PMCPMC8919469
OpenAlexW4220946180

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.