Evidence map›Paper›PMID 39677819›Full record

ArticlebioRxiv : the preprint server for biology2024

A TROP2/Claudin Program Mediates Immune Exclusion to Impede Checkpoint Blockade in Breast Cancer.

Bogang Wu, Win Thant, Elena Bitman, Ting Liu, Jie Liu, Eleftherios I Paschalis, Katherine H Xu, Linda T Nieman, David T Ting, Nayana Thimmiah and 6 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors.

Bogang WuMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA.ORCID 0000-0003-1654-198X
Win ThantMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA.
Elena BitmanMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA.
Ting LiuMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA.
Jie LiuMassachusetts Eye and Ear, Harvard Medical School, Boston, MA, 02114, USA.
Eleftherios I PaschalisMassachusetts Eye and Ear, Harvard Medical School, Boston, MA, 02114, USA.
Katherine H XuMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA.
Linda T NiemanMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA.
David T TingMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA.
Nayana ThimmiahMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA.
Sheng SunMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA.
Rachel O AbelmanMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA.
Steven J IsakoffMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA.
Laura M SpringMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA.
Aditya BardiaMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA.
Leif W EllisenMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA.

Funding

Synergistic combinatorial DNA damage response/repair inhibition and Sacituzumab Govitecan in triple-negative breast cancerR01CA260890 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI Aditya Bardia, LEIF W ELLISEN · 2022 to 2026
$2.8M
Breaching the Tumor-Immune Mechanical Barrier for Optimal Antitumor ImmunityK99CA286969 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI WU, BOGANG · 2024 to 2025
$352k
NCI NIH HHS K99 CA286969NCI NIH HHS R01 CA260890
6 · The paper itself

Abstract

Immune exclusion inhibits anti-tumor immunity and response to immunotherapy, but its mechanisms remain poorly defined. Here, we demonstrate that Trophoblast Cell-Surface Antigen 2 (TROP2), a key target of emerging anti-cancer Antibody Drug Conjugates (ADCs), controls barrier-mediated immune exclusion in Triple-Negative Breast Cancer (TNBC) through Claudin 7 association and tight junction regulation. TROP2 expression is inversely correlated with T cell infiltration and strongly associated with outcomes in TNBC. Loss-of-function and reconstitution experiments demonstrate TROP2 is sufficient to drive tumor progression in vivo in a CD8 T cell-dependent manner, while its loss deregulates expression and localization of multiple tight junction proteins, enabling T cell infiltration. Employing a humanized TROP2 syngeneic TNBC model, we show that TROP2 targeting via hRS7, the antibody component of Sacituzumab govitecan (SG), enhances the anti-PD1 response associated with improved T cell accessibility and effector function. Correspondingly, TROP2 expression is highly associated with lack of response to anti-PD1 therapy in human breast cancer. Thus, TROP2 controls an immune exclusion program that can be targeted to enhance immunotherapy response.

Indexed as

Antibody-Drug Conjugateantitumor immunityimmune checkpoint blockadeimmune exclusionPD-1sacituzumab govitecantight junctiontriple negative breast cancerTROP2tumor immune microenvironment

Identifiers

PMID39677819
PMCPMC11642930

What OpenQuestion holds

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LicenceCC BY-NC
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.