Evidence map›Paper›PMID 24942756›Full record

Trial reportCancer immunology research2014

Immunotherapy converts nonimmunogenic pancreatic tumors into immunogenic foci of immune regulation.

Eric R Lutz, Annie A Wu, Elaine Bigelow, Rajni Sharma, Guanglan Mo, Kevin Soares, Sara Solt, Alvin Dorman, Anthony Wamwea, Allison Yager and 7 more

Open access · bronzeAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Cancer immunology research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 347 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
347citing papers in PubMed, 2 pooled it
19.5field-weighted citation impact, top 1% 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

347 citing papers in PubMed, 2 syntheses or guidelines pooled it, 535 citations in OpenAlex.

  1. Pooled it
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  10. Evaluation of Cyclophosphamide/GVAX Pancreas Followed by Listeria-Mesothelin (CRS-207) with or without Nivolumab in Patients with Pancreatic Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020
    Trial
  11. Review
  12. Review
  13. A Phase II Trial of Pembrolizumab plus Granulocyte-Macrophage Colony-Stimulating Factor in Advanced Biliary Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
    Article
  14. Article
  15. Article
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  18. Review
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287 more citing papers are in PubMed but not listed here.

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

17 authors at 3 institutions in 1 country.

Eric R LutzAuthors' Affiliations: Departments of Oncology, The Sidney Kimmel Cancer Center; The Skip Viragh Center for Pancreatic Cancer Research and Clinical Care; The Sol Goldman Pancreatic Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland; and.
Annie A WuAuthors' Affiliations: Departments of Oncology, Surgery; The Sidney Kimmel Cancer Center;
Elaine BigelowAuthors' Affiliations: Departments of Oncology, The Sidney Kimmel Cancer Center;
Rajni SharmaPathology, and.
Guanglan MoAuthors' Affiliations: Departments of Oncology, The Sidney Kimmel Cancer Center; The Skip Viragh Center for Pancreatic Cancer Research and Clinical Care;
Kevin SoaresAuthors' Affiliations: Departments of Oncology, Surgery; The Sidney Kimmel Cancer Center; The Skip Viragh Center for Pancreatic Cancer Research and Clinical Care; The Sol Goldman Pancreatic Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland; and.
Sara SoltAuthors' Affiliations: Departments of Oncology, The Sidney Kimmel Cancer Center; The Skip Viragh Center for Pancreatic Cancer Research and Clinical Care;
Alvin DormanAuthors' Affiliations: Departments of Oncology, The Sidney Kimmel Cancer Center; The Skip Viragh Center for Pancreatic Cancer Research and Clinical Care;
Anthony WamweaAuthors' Affiliations: Departments of Oncology, The Sidney Kimmel Cancer Center; The Skip Viragh Center for Pancreatic Cancer Research and Clinical Care;
Allison YagerAuthors' Affiliations: Departments of Oncology, The Sidney Kimmel Cancer Center;
Daniel LaheruAuthors' Affiliations: Departments of Oncology, The Sidney Kimmel Cancer Center; The Skip Viragh Center for Pancreatic Cancer Research and Clinical Care;
Christopher L WolfgangAuthors' Affiliations: Departments of Oncology, Surgery; The Sidney Kimmel Cancer Center; The Sol Goldman Pancreatic Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland; and.
Jiang WangDepartment of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio.
Ralph H HrubanAuthors' Affiliations: Departments of Oncology, Pathology, and The Sidney Kimmel Cancer Center; The Sol Goldman Pancreatic Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland; and.
Robert A AndersAuthors' Affiliations: Departments of Oncology, Pathology, and The Sidney Kimmel Cancer Center; The Sol Goldman Pancreatic Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland; and.
Elizabeth M JaffeeAuthors' Affiliations: Departments of Oncology, Pathology, and The Sidney Kimmel Cancer Center; The Skip Viragh Center for Pancreatic Cancer Research and Clinical Care; The Sol Goldman Pancreatic Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland; and lzheng6@jhmi.edu ejaffee@jhmi.edu.
Lei ZhengAuthors' Affiliations: Departments of Oncology, Surgery; The Sidney Kimmel Cancer Center; The Skip Viragh Center for Pancreatic Cancer Research and Clinical Care; The Sol Goldman Pancreatic Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland; and lzheng6@jhmi.edu ejaffee@jhmi.edu.
Sidney Kimmel Cancer Center · USJohns Hopkins University · USUniversity of Cincinnati Medical Center · US

Funding

Tumor Antigens for Individual Signatures and TherapyP50CA062924 · NCI · JOHNS HOPKINS UNIVERSITY · PI JAFFEE, ELIZABETH M. · 1993 to 2022
$54.6M
TRANSGENIC MODELS FOR PROSTATE CANCER AND AUTOIMMUNITYP50CA058236 · NCI · JOHNS HOPKINS UNIVERSITY · PI ISAACS, JOHN TOD · 1992 to 2020
$43.9M
Interrogate the interaction between tumor cells and nerves in the tumor microenvironment of pancreatic cancerR01CA169702 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI ZHENG, LEI · 2013 to 2023
$3.6M
Dissecting the mechanisms of immune tolerance within the pancreatic tumor's microK23CA148964 · NCI · JOHNS HOPKINS UNIVERSITY · PI ZHENG, LEI · 2010 to 2014
$888k
NCI NIH HHS K23 CA148964NCI NIH HHS K23 CA148964-01NCI NIH HHS P50 CA058236NCI NIH HHS P50 CA062924NCI NIH HHS R01 CA169702
6 · The paper itself

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is considered a "nonimmunogenic" neoplasm. Single-agent immunotherapies have failed to demonstrate significant clinical activity in PDAC and other "nonimmunogenic" tumors, in part due to a complex tumor microenvironment (TME) that provides a formidable barrier to immune infiltration and function. We designed a neoadjuvant and adjuvant clinical trial comparing an irradiated, granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting, allogeneic PDAC vaccine (GVAX) given as a single agent or in combination with low-dose cyclophosphamide to deplete regulatory T cells (Treg) as a means to study how the TME is altered by immunotherapy. Examination of resected PDACs revealed the formation of vaccine-induced intratumoral tertiary lymphoid aggregates in 33 of 39 patients 2 weeks after vaccine treatment. Immunohistochemical analysis showed these aggregates to be regulatory structures of adaptive immunity. Microarray analysis of microdissected aggregates identified gene-expression signatures in five signaling pathways involved in regulating immune-cell activation and trafficking that were associated with improved postvaccination responses. A suppressed Treg pathway and an enhanced Th17 pathway within these aggregates were associated with improved survival, enhanced postvaccination mesothelin-specific T-cell responses, and increased intratumoral Teff:Treg ratios. This study provides the first example of immune-based therapy converting a "nonimmunogenic" neoplasm into an "immunogenic" neoplasm by inducing infiltration of T cells and development of tertiary lymphoid structures in the TME. Post-GVAX T-cell infiltration and aggregate formation resulted in the upregulation of immunosuppressive regulatory mechanisms, including the PD-1-PD-L1 pathway, suggesting that patients with vaccine-primed PDAC may be better candidates than vaccine-naïve patients for immune checkpoint and other immunomodulatory therapies.

Indexed as

AdenocarcinomaAntineoplastic Agents, AlkylatingCancer VaccinesCell AggregationChemotherapy, AdjuvantCyclophosphamideDrug Administration ScheduleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansInterferon-gammaLymphocyte ActivationLymphocytes, Tumor-InfiltratingPancreatic NeoplasmsT-Lymphocytes, RegulatoryUp-RegulationAntineoplastic Agents, AlkylatingCancer VaccinesCyclophosphamideGVAX vaccineInterferon-gamma

Identifiers

PMID24942756
PMCPMC4082460
OpenAlexW2169410102

What OpenQuestion holds

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LicenceTDM
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.