Evidence map›Paper›PMID 42771495›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2026

Key regulatory elements of the TGFβ-LRRC15 axis predict disease progression and immunotherapy resistance across cancer types.

Michael Cheng, Claire M Storey, Mohamed Altai, Julie E Park, Julie Tran, Smiths S Lueong, Daniel Thorek, Liqun Mao, Wahed Zedan, Constance Yuen and 10 more

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Key regulatory elements of the TGFβ-LRRC15 axis predict disease progression and immunotherapy resistance across cancer types.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  2. Review
  3. Article
  4. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors.

Michael Cheng *Bioinformatics Interdepartmental Program, University of California Los Angeles, Los Angeles, CA.ORCID 0000-0002-1869-2557
Claire M Storey *Department of Molecular & Medical Pharmacology, University of California Los Angeles, Los Angeles, CA.ORCID 0000-0003-0792-1569
Mohamed AltaiDivision of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund, Sweden.
Julie E ParkDepartment of Molecular & Medical Pharmacology, University of California Los Angeles, Los Angeles, CA.
Julie TranDepartment of Integrative Biology & Physiology, University of California Los Angeles, Los Angeles, CA.ORCID 0009-0001-6031-3899
Smiths S LueongGerman Cancer Consortium (DKTK), partner site Essen, a partnership between German Cancer Research Center (DKFZ) and University Hospital Essen, Essen, Germany.
Daniel ThorekDepartment of Radiology, Washington University School of Medicine, St. Louis, MO.ORCID 0000-0003-2437-1239
Liqun MaoDepartment of Molecular & Medical Pharmacology, University of California Los Angeles, Los Angeles, CA.ORCID 0000-0001-9704-3995
Wahed ZedanDivision of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund, Sweden.ORCID 0000-0002-0287-5367
Constance YuenDepartment of Molecular & Medical Pharmacology, University of California Los Angeles, Los Angeles, CA.ORCID 0000-0001-9714-9001
Alexander RidleyDepartment of Molecular & Medical Pharmacology, University of California Los Angeles, Los Angeles, CA.
Marija Trajkovic-ArsicGerman Cancer Consortium (DKTK), partner site Essen, a partnership between German Cancer Research Center (DKFZ) and University Hospital Essen, Essen, Germany.
Ken HerrmannDepartment of Nuclear Medicine, University Hospital Essen, University of Duisburg-Essen, DKTK, Essen, Germany.ORCID 0000-0002-9662-7259
Sumit K SubudhiDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.
Bilal A SiddiquiDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID 0000-0002-6806-1294
Katharina LückerathDepartment of Nuclear Medicine, University Hospital Essen, University of Duisburg-Essen, DKTK, Essen, Germany.
Jens T SivekeGerman Cancer Consortium (DKTK), partner site Essen, a partnership between German Cancer Research Center (DKFZ) and University Hospital Essen, Essen, Germany.ORCID 0000-0002-8772-4778
Robert DamoiseauxDepartment of Molecular & Medical Pharmacology, University of California Los Angeles, Los Angeles, CA.
Xia YangBioinformatics Interdepartmental Program, University of California Los Angeles, Los Angeles, CA.ORCID 0000-0002-3971-038X
David UlmertDepartment of Molecular & Medical Pharmacology, University of California Los Angeles, Los Angeles, CA.ORCID 0000-0002-7871-2281

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Transforming growth factor-beta (TGFβ) has dual roles in cancer, initially suppressing tumors but later promoting metastasis and immune evasion. Efforts to inhibit TGFβ have been largely unsuccessful due to significant toxicity and indiscriminate immunosuppression. Leucine-rich repeat-containing protein 15 (LRRC15) is a TGFβ-regulated antigen expressed by cancer cells of mesenchymal origin and cancer-associated fibroblasts (CAFs). In preclinical studies, ablation of TGFβ-driven LRRC15+ CAFs enhances effector functions of CD8+ T cells. However, the pathobiological mechanisms associated with TGFβ's upregulation of LRRC15 expression in cancer cells remain unclear. Using an integrated approach combining functional compound screening with scRNA-seq, we reveal key genomic features regulating TGFβ's ability to increase LRRC15 expression on cancer cells. Construction of gene regulatory networks converged our analyses on four key genes (

Indexed as

Drug Resistance, NeoplasmImmunotherapyMembrane ProteinsNeoplasmsTransforming Growth Factor betaAnimalsCancer-Associated FibroblastsCell Line, TumorDisease ProgressionGene Expression Regulation, NeoplasticGene Regulatory NetworksHumansSignal TransductionMembrane ProteinsTransforming Growth Factor betaimmunosuppressionLRRC15TGFB

Identifiers

PMID42771495
PMCPMC13624622

What OpenQuestion holds

Textmetadata
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.