Evidence map›Paper›PMID 29746929›Full record

ArticleCancer letters2018

Trastuzumab upregulates PD-L1 as a potential mechanism of trastuzumab resistance through engagement of immune effector cells and stimulation of IFNγ secretion.

Bharat K R Chaganty, Songbo Qiu, Anneliese Gest, Yang Lu, Cristina Ivan, George A Calin, Louis M Weiner, Zhen Fan

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer letters, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 128 papers.

0numbers the graph read from it
0cells of the map it votes in
128citing papers in PubMed
5.0field-weighted citation impact, top 3% 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

128 citing papers in PubMed, 194 citations in OpenAlex.

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  4. Neoadjuvant camrelizumab plus trastuzumab and chemotherapy for HER2-positive gastric or gastroesophageal junction adenocarcinoma: a single-arm, phase 2 trial.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2025
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  16. Advances in Targeting HER2 across Cancer Subtypes: A Pan-Tumor Approach.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
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68 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

8 authors at 2 institutions in 1 country.

Bharat K R ChagantyDepartment of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX 77030, USA.
Songbo QiuDepartment of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Anneliese GestDepartment of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Yang LuDepartment of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Cristina IvanDepartment of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
George A CalinDepartment of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX 77030, USA.
Louis M WeinerLombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057, USA.
Zhen FanDepartment of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX 77030, USA. Electronic address: zfan@mdanderson.org.
The University of Texas MD Anderson Cancer Center · USGeorgetown University · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
A novel targeted therapy for HNSCC based on a novel activity of cetuximabR01CA179015 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI FAN, ZHEN · 2014 to 2018
$1.7M
Mechanisms of tumor resistance to anti-HER/ErbB therapeuticsR01CA129036 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI FAN, ZHEN · 2008 to 2012
$1.6M
NCI NIH HHS P30 CA016672NCI NIH HHS R01 CA129036NCI NIH HHS R01 CA179015
6 · The paper itself

Abstract

Here, we report that treatment of syngeneic mouse tumors transduced to overexpress human epidermal growth factor receptor-2 (HER2) with the anti-human HER2 antibody trastuzumab upregulated the level of programmed death-ligand 1 (PD-L1), an important negative regulator of T-cell response, in a transgenic mouse model immune-tolerant to human HER2. We further found that trastuzumab alone had no detectable effect on the level of PD-L1 expression in monocultures of HER2-overexpressing human breast cancer cells but upregulated PD-L1 in the same panel of HER2-overexpressing breast cancer cells when they were co-cultured with human peripheral blood mononuclear cells, and the upregulation of PD-L1 could be blocked by an IFNγ-neutralizing antibody. Inhibition of HER2 intrinsic signaling via HER2 expression knockdown or kinase inhibition had variable and cell-context-specific effects on downregulating the PD-L1 level. Analysis of The Cancer Genome Atlas database showed no direct correlation between HER2 and PD-L1 at the messenger RNA level. Trastuzumab-mediated upregulation of PD-L1 through engagement of immune effector cells may function as a potential mechanism of trastuzumab resistance. Our data justify further investigation of the value of adding anti-PD-1 or anti-PD-L1 therapy to trastuzumab-based treatment.

Indexed as

AnimalsAntineoplastic Agents, ImmunologicalB7-H1 AntigenBreast NeoplasmsCell Culture TechniquesCell Line, TumorCoculture TechniquesDrug Resistance, NeoplasmErb-b2 Receptor Tyrosine KinasesFemaleGene Expression Regulation, NeoplasticGene Knockdown TechniquesHumansInterferon-gammaLeukocytes, MononuclearMelanoma, ExperimentalAntineoplastic Agents, ImmunologicalB7-H1 AntigenCD274 protein, humanERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesIFNG protein, humanInterferon-gammaRNA, MessengerTrastuzumabBreast cancerHER2IFNγPD-L1Trastuzumab

Identifiers

PMID29746929
PMCPMC6004098
OpenAlexW2801657532

What OpenQuestion holds

Textmetadata
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.