Evidence mapPaperPMID 37534996Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2023

Treatment Response in First-Line Metastatic Pancreatic Ductal Adenocarcinoma Is Stratified By a Composite Index of Tumor Proliferation and CD8 T-Cell Infiltration.

Gregory L Beatty, Devora Delman, Jiayi Yu, Mingen Liu, Joey H Li, Liti Zhang, Jae W Lee, Renee B Chang, Nathan Bahary, Eugene P Kennedy and 3 more

Registry-linked trialOpen access · greenAbstract read
In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02077881 (A Phase I/II Study of Indoximod in Combination With Gemcitabine and Nab-Paclitaxel in Patients With Metastatic Adenocarcinoma of the Pancreas), which is not on this map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
2.5field-weighted citation impact, top 10% 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.

NCT02077881 phase1 / phase2completednot on this map

A Phase I/II Study of Indoximod in Combination With Gemcitabine and Nab-Paclitaxel in Patients With Metastatic Adenocarcinoma of the Pancreas

TypeinterventionalSponsorNewLink Genetics CorporationRan2014 to 2018Enrolled157ConditionsMetastatic Pancreatic Adenocarcinoma, Metastatic Pancreatic CancerArmsNab-Paclitaxel, Gemcitabine, Indoximod
3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 11 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Review
  5. Review
  6. Updates in Molecular Profiling of Pancreatic Ductal Adenocarcinoma.The Surgical clinics of North America · 2024
    Review
  7. Article
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

13 authors at 6 institutions in 1 country.

Gregory L BeattyAbramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania.ORCID 0000-0001-7165-5993
Devora Delman *Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania.ORCID 0000-0003-1283-6705
Jiayi Yu *Newlink Genetics (now LUMOS Pharmaceuticals), Ames, Iowa.ORCID 0009-0004-4284-5615
Mingen LiuAbramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania.ORCID 0009-0000-0790-0456
Joey H LiAbramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania.ORCID 0000-0002-3865-5876
Liti ZhangAbramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania.ORCID 0009-0003-5645-5063
Jae W LeeDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.ORCID 0000-0002-0735-5707
Renee B ChangAbramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania.ORCID 0000-0001-6298-7005
Nathan BaharyDepartment of Hematology-Oncology, Allegheny Health Network Cancer Institute, Pittsburgh, Pennsylvania.ORCID 0009-0005-3900-816X
Eugene P KennedyNewlink Genetics (now LUMOS Pharmaceuticals), Ames, Iowa.ORCID 0009-0008-7418-3774
Andrea Wang-GillamDivision of Oncology, Department of Internal Medicine, Washington University in St. Louis, St. Louis, Missouri.ORCID 0000-0003-0458-7614
Gabriela R RossiNewlink Genetics (now LUMOS Pharmaceuticals), Ames, Iowa.ORCID 0009-0003-4526-7278
Ignacio Garrido-LagunaUniversity of Utah Huntsman Cancer Institute, Salt Lake City, Utah.ORCID 0000-0003-2273-9028
University of Pennsylvania · USNewLink Genetics (United States) · USAllegheny Health Network · USHuntsman Cancer Institute · USJohns Hopkins University · USWashington University in St. Louis · US

Funding

MULTIDISCIPLINARY TRAINING IN MICROBIAL PATHOGENESIST32AI007323 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Peter John Bradley · 1988 to 2026
$8.6M
Targeting the liver for immunotherapy in pancreatic cancerR01CA197916 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Gregory L Beatty · 2016 to 2026
$3.7M
Stopping PDA progression using inhibitors of CSC dissemination and immunotherapyU01CA224193 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI HINGORANI, SUNIL R · 2017 to 2021
$3.3M
Mechanisms and therapeutic targets of cancer metastasisR01CA245323 · NCI · UNIVERSITY OF PENNSYLVANIA · PI BEATTY, GREGORY L · 2020 to 2024
$1.8M
NCI NIH HHS R01 CA197916NCI NIH HHS R01 CA245323NCI NIH HHS U01 CA224193NIAID NIH HHS T32 AI007323
6 · The paper itself

Abstract

purposeDeterminants of treatment outcomes to chemotherapy-based regimens in metastatic pancreatic ductal adenocarcinoma (PDA) remain ill-defined. Our aim was to examine tissue-based correlates of treatment response and resistance using matched baseline and on-treatment biopsies collected from patients with PDA treated in the first-line metastatic setting. EXPERIMENTAL

designPatients with treatment-naïve metastatic PDA were enrolled in a Phase II trial (NCT02077881) investigating gemcitabine plus nab-paclitaxel in combination with indoximod, an orally administered small-molecule inhibitor of the IDO pathway. Baseline and on-treatment biopsies (week 8) of metastatic lesions (88% liver) were collected from a cohort of responders (N = 8) and non-responders (N = 8) based on RECIST v1.1 and examined by multiplex IHC and mRNA sequencing.

resultsTreatment altered the transcriptional profile of metastatic lesions with a decrease in tumor cell proliferation independent of treatment response. The antiproliferative response was seen in both basal and classical PDA subtypes. PDA subtype was not associated with survival outcomes; instead, genes involved in immune activation distinguished responders from non-responders. Tumor response was associated with an increase in CD3+ and CD8+ T-cell infiltrates into metastatic lesions. A composite of decreased tumor proliferation in response to treatment and increased CD8 T-cell infiltration in metastatic lesions identified responders and associated with a favorable survival outcome.

conclusionsOur findings suggest that inhibiting cancer cell proliferation alone in PDA is insufficient to produce tumor responses and support a role for tumor-extrinsic mechanisms, such as CD8+ T cells, which combine with the cancer cell proliferation index to define treatment outcomes.

Indexed as

AdenocarcinomaCarcinoma, Pancreatic DuctalPancreatic NeoplasmsAlbuminsAntineoplastic Combined Chemotherapy ProtocolsCD8-Positive T-LymphocytesDeoxycytidineHumansPaclitaxelAlbuminsDeoxycytidinePaclitaxel

Identifiers

PMID37534996
PMCPMC10530235
OpenAlexW4385514235

What Socratic holds

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Registered trials

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 Socratic graph.