Evidence map›Paper›PMID 32429929›Full record

ArticleBMC cancer2020

Exploratory analysis of immune checkpoint receptor expression by circulating T cells and tumor specimens in patients receiving neo-adjuvant chemotherapy for operable breast cancer.

Robert Wesolowski, Andrew Stiff, Dionisia Quiroga, Christopher McQuinn, Zaibo Li, Hiroaki Nitta, Himanshu Savardekar, Brooke Benner, Bhuvaneswari Ramaswamy, Maryam Lustberg and 12 more

Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in BMC cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04022616 (Myeloid-Derived Suppressor Cell Function in Breast Cancer Patients), which is not on this map. Cited by 12 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed, 1 pooled it
0.9field-weighted citation impact, top 23% 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.

NCT04022616 recruitingnot on this map

Myeloid-Derived Suppressor Cell Function in Breast Cancer Patients

TypeobservationalSponsorOhio State University Comprehensive Cancer CenterRan2010 to 2027Enrolled99ConditionsBreast CancerArmsSpecimen collection
3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.

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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

22 authors at 3 institutions in 1 country.

Robert WesolowskiThe Ohio State University Comprehensive Cancer Center, The Ohio State University, 410 W 12th Avenue, Columbus, OH, 43210, USA. Robert.Wesolowski@osumc.edu.ORCID http://orcid.org/0000-0003-0606-0648
Andrew StiffThe Ohio State University Comprehensive Cancer Center, The Ohio State University, 410 W 12th Avenue, Columbus, OH, 43210, USA.
Dionisia QuirogaThe Ohio State University Comprehensive Cancer Center, The Ohio State University, 410 W 12th Avenue, Columbus, OH, 43210, USA.
Christopher McQuinnThe Ohio State University Comprehensive Cancer Center, The Ohio State University, 410 W 12th Avenue, Columbus, OH, 43210, USA.
Zaibo LiDepartment of Pathology, The Ohio State University, 410 W 10th Ave, N337B Doan Hall, Columbus, OH, 43210, USA.
Hiroaki NittaRoche Tissue Diagnostics, 1910 E. Innovation Park Drive, Tucson, AZ, 85744, USA.
Himanshu SavardekarThe Ohio State University Comprehensive Cancer Center, The Ohio State University, 410 W 12th Avenue, Columbus, OH, 43210, USA.
Brooke BennerThe Ohio State University Comprehensive Cancer Center, The Ohio State University, 410 W 12th Avenue, Columbus, OH, 43210, USA.
Bhuvaneswari RamaswamyDepartment of Internal Medicine, Division of Medical Oncology, The Ohio State University, Starling Loving Hall, 320 W10th Ave, Columbus, OH, 43210, USA.
Maryam LustbergDepartment of Internal Medicine, Division of Medical Oncology, The Ohio State University, Starling Loving Hall, 320 W10th Ave, Columbus, OH, 43210, USA.
Rachel M LaymanDepartment of Internal Medicine, Division of Medical Oncology, The Ohio State University, Starling Loving Hall, 320 W10th Ave, Columbus, OH, 43210, USA.
Erin MacraeDepartment of Internal Medicine, Division of Medical Oncology, The Ohio State University, Starling Loving Hall, 320 W10th Ave, Columbus, OH, 43210, USA.
Mahmoud KassemThe Ohio State University Comprehensive Cancer Center, The Ohio State University, 410 W 12th Avenue, Columbus, OH, 43210, USA.
Nicole WilliamsDepartment of Internal Medicine, Division of Medical Oncology, The Ohio State University, Starling Loving Hall, 320 W10th Ave, Columbus, OH, 43210, USA.
Sagar SardesaiDepartment of Internal Medicine, Division of Medical Oncology, The Ohio State University, Starling Loving Hall, 320 W10th Ave, Columbus, OH, 43210, USA.
Jeffrey VanDeusenDepartment of Internal Medicine, Division of Medical Oncology, The Ohio State University, Starling Loving Hall, 320 W10th Ave, Columbus, OH, 43210, USA.
Daniel StoverDepartment of Internal Medicine, Division of Medical Oncology, The Ohio State University, Starling Loving Hall, 320 W10th Ave, Columbus, OH, 43210, USA.
Mathew CherianDepartment of Internal Medicine, Division of Medical Oncology, The Ohio State University, Starling Loving Hall, 320 W10th Ave, Columbus, OH, 43210, USA.
Thomas A MaceThe Ohio State University Comprehensive Cancer Center, The Ohio State University, 410 W 12th Avenue, Columbus, OH, 43210, USA.
Lianbo YuCenter for Biostatistics, The Ohio State University, 2012 Kenny Rd, Columbus, OH, 43221, USA.
Megan DugganThe Ohio State University Comprehensive Cancer Center, The Ohio State University, 410 W 12th Avenue, Columbus, OH, 43210, USA.
William E CarsonThe Ohio State University Comprehensive Cancer Center, The Ohio State University, 410 W 12th Avenue, Columbus, OH, 43210, USA.
The Ohio State University · USRoche (United States) · USThe Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute · US

Funding

TWO SIGNAL REQUIREMENT FOR NATURAL KILLER IMMUNITYP01CA095426 · NCI · OHIO STATE UNIVERSITY · PI BYRD, JOHN C. · 2002 to 2016
$29.6M
Translational Training Grant in Experimental TherapeuticsK12CA133250 · NCI · OHIO STATE UNIVERSITY · PI WILLIAM E. CARSON, Rosa Lapalombella · 2008 to 2026
$15.0M
The Ohio State University Center for Clinical and Translational Science (UL1)UL1TR000090 · NCATS · OHIO STATE UNIVERSITY · PI JACKSON, REBECCA D · 2012 to 2013
$7.9M
Integrative Training in Biomedical SystemsT32GM068412 · NIGMS · OHIO STATE UNIVERSITY · PI PARVIN, JEFFREY D · 2005 to 2020
$2.4M
NCATS NIH HHS UL1TR000090NCI NIH HHS 2K12CA133250-11NCI NIH HHS 2P01CA095426-11NCI NIH HHS K12 CA133250NIGMS NIH HHS T32 GM068412
6 · The paper itself

Abstract

backgroundWhile combinations of immune checkpoint (ICP) inhibitors and neo-adjuvant chemotherapy (NAC) have begun testing in patients with breast cancer (BC), the effects of chemotherapy on ICP expression in circulating T cells and within the tumor microenvironment are still unclear. This information could help with the design of future clinical trials by permitting the selection of the most appropriate ICP inhibitors for incorporation into NAC.

methodsPeripheral blood samples and/or tumor specimens before and after NAC were obtained from 24 women with operable BC. The expression of CTLA4, PD-1, Lag3, OX40, and Tim3 on circulating T lymphocytes before and at the end of NAC were measured using flow cytometry. Furthermore, using multi-color immunohistochemistry (IHC), the expression of immune checkpoint molecules by stromal tumor-infiltrating lymphocytes (TILs), CD8+ T cells, and tumor cells was determined before and after NAC. Differences in the percentage of CD4+ and CD8+ T cells expressing various checkpoint receptors were determined by a paired Student's t-test.

resultsThis analysis showed decreased ICP expression by circulating CD4+ T cells after NAC, including significant decreases in CTLA4, Lag3, OX40, and PD-1 (all p values < 0.01). In comparison, circulating CD8+ T cells showed a significant increase in CTLA4, Lag3, and OX40 (all p values < 0.01). Within tumor samples, TILs, CD8+ T cells, and PD-L1/PD-1 expression decreased after NAC. Additionally, fewer tumor specimens were considered to be PD-L1/PD-1 positive post-NAC as compared to pre-NAC biopsy samples using a cutoff of 1% expression.

conclusionsThis work revealed that NAC treatment can substantially downregulate CD4+ and upregulate CD8+ T cell ICP expression as well as deplete the amount of TILs and CD8+ T cells found in breast tumor samples. These findings provide a starting point to study the biological significance of these changes in BC patients.

trial registrationNCT04022616.

Indexed as

AdultAgedAntineoplastic Combined Chemotherapy ProtocolsB7-H1 AntigenBiomarkers, TumorBreast NeoplasmsCD8-Positive T-LymphocytesChemotherapy, AdjuvantFemaleFollow-Up StudiesGene Expression Regulation, NeoplasticHumansLymphocytes, Tumor-InfiltratingMiddle AgedNeoadjuvant TherapyPrognosisB7-H1 AntigenBiomarkers, TumorCD274 protein, humanPDCD1 protein, humanProgrammed Cell Death 1 ReceptorBreast cancerCD8+ T cellsImmune checkpoint receptorsTumor-infiltrating lymphocytes

Identifiers

PMID32429929
PMCPMC7236344
OpenAlexW3028403973

What OpenQuestion holds

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LicenceCC BY
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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 OpenQuestion graph.