Evidence map›Paper›PMID 39577413›Full record

ArticleImmunity2024

Cancer cells restrict immunogenicity of retrotransposon expression via distinct mechanisms.

Siyu Sun, Eunae You, Jungeui Hong, David Hoyos, Isabella Del Priore, Kaloyan M Tsanov, Om Mattagajasingh, Andrea Di Gioacchino, Sajid A Marhon, Jonathan Chacon-Barahona and 22 more

Abstract read
In one paragraph

Article in Immunity, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing 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

27 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Review
  6. Review
  7. The Dynamic Alliance of p53 and Metabolism in the Tumor Microenvironment Shapes Tumor Evolution.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026
    Review
  8. Evolution ofInternational journal of molecular sciences · 2026
    Review
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. NNature reviews. Cancer · 2026
    Review
  15. Review
  16. Article
  17. Revisiting Clonal Evolution Through the Light of Retrotransposons.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025
    Review
  18. Article
  19. Review
  20. 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

32 authors.

Siyu SunHalvorsen Center for Computational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: suns3@mskcc.org.
Eunae YouMassachusetts General Cancer Center, Harvard Medical School, Charlestown, MA, USA.
Jungeui HongDavid M. Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
David HoyosTri-Institutional Program in Computational Biology and Medicine, Weill Cornell Medicine, New York, NY, USA.
Isabella Del PrioreLouis V. Gerstner Jr. Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Kaloyan M TsanovCancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Om MattagajasinghDepartment of Biochemistry and Molecular Medicine, Université de Montréal, Montreal, QC, Canada.
Andrea Di GioacchinoLaboratoire de Physique de l'Ecole Normale Supérieure, Sorbonne Université, Université de Paris, Paris, France.
Sajid A MarhonPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Jonathan Chacon-BarahonaTri-Institutional Program in Computational Biology and Medicine, Weill Cornell Medicine, New York, NY, USA.
Hao LiHalvorsen Center for Computational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Hua JiangLaboratory of Cellular and Structural Biology, The Rockefeller University, New York, NY, USA.
Samira HozeifiEuropean Research Institute for the Biology of Ageing, University Medical Center Groningen, Groningen, The Netherlands.
Omar Rosas-BringasEuropean Research Institute for the Biology of Ageing, University Medical Center Groningen, Groningen, The Netherlands.
Katherine H XuMassachusetts General Cancer Center, Harvard Medical School, Charlestown, MA, USA.
Yuhui SongMassachusetts General Cancer Center, Harvard Medical School, Charlestown, MA, USA.
Evan R LangMassachusetts General Cancer Center, Harvard Medical School, Charlestown, MA, USA.
Alexandra S RojasMassachusetts General Cancer Center, Harvard Medical School, Charlestown, MA, USA.
Linda T NiemanMassachusetts General Cancer Center, Harvard Medical School, Charlestown, MA, USA.
Bidish K PatelMassachusetts General Cancer Center, Harvard Medical School, Charlestown, MA, USA.
Rajmohan MuraliLast Wish Program and Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Pharto ChandaLast Wish Program and Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Ali KaracayLast Wish Program and Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Nicolas VabretPrecision Immunology Institute at the Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Daniel D De CarvalhoPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
Daniel ZenklusenDepartment of Biochemistry and Molecular Medicine, Université de Montréal, Montreal, QC, Canada.
John LaCavaPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada; European Research Institute for the Biology of Ageing, University Medical Center Groningen, Groningen, The Netherlands.
Scott W LoweCancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA.
David T TingMassachusetts General Cancer Center, Harvard Medical School, Charlestown, MA, USA.
Christine A Iacobuzio-DonahueDavid M. Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Last Wish Program and Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Alexander SolovyovHalvorsen Center for Computational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Benjamin D GreenbaumHalvorsen Center for Computational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Physiology, Biophysics & Systems Biology, Weill Cornell Medicine, New York, NY, USA. Electronic address: greenbab@mskcc.org.

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4M
VIRAL TRANSACTIVATIONP01CA013106 · NCI · COLD SPRING HARBOR LABORATORY · PI William Richard McCombie · 1985 to 2026
$116.8M
Vaccine FacilityP30CA016087 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI MARK Reid PHILIPS · 1985 to 2026
$83.1M
Interrogating the Evolutionary Dynamics of Cancer for Clinical Benefit and ActionabilityR35CA220508 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI IACOBUZIO-DONAHUE, CHRISTINE A · 2018 to 2024
$6.9M
Modulating anti-HIV immunity by plasmacytoid dendritic cellsR01AI081848 · NIAID · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI BHARDWAJ, NINA · 2010 to 2021
$4.5M
Defining molecular contributions of LINE-1 retrotransposons to AD / ADRDR01AG078925 · NIA · ROCKEFELLER UNIVERSITY · PI John LaCava, John M Sedivy · 2022 to 2026
$3.7M
Understanding the Relationship of Repeat Expression and MetastasisR01CA240924 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI GREENBAUM, BENJAMIN, TING, DAVID TSAI · 2019 to 2023
$3.3M
A Statistical Physics Framework for Understanding the Role of Repeat RNA in Tumor ImmunityU01CA228963 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI GREENBAUM, BENJAMIN, TING, DAVID TSAI · 2020 to 2024
$3.2M
Demonstrating interactome-level connections between Alzheimer disease, LINE-1 retrotransposons, and cellular senescenceR01GM126170 · NIGMS · ROCKEFELLER UNIVERSITY · PI LACAVA, JOHN · 2018 to 2021
$2.4M
Howard Hughes Medical InstituteNCI NIH HHS P01 CA013106NCI NIH HHS P30 CA008748NCI NIH HHS P30 CA016087NCI NIH HHS R01 CA240924NCI NIH HHS R35 CA220508NCI NIH HHS U01 CA228963NIAID NIH HHS R01 AI081848NIA NIH HHS R01 AG078925NIGMS NIH HHS R01 GM126170
6 · The paper itself

Abstract

To thrive, cancer cells must navigate acute inflammatory signaling accompanying oncogenic transformation, such as via overexpression of repeat elements. We examined the relationship between immunostimulatory repeat expression, tumor evolution, and the tumor-immune microenvironment. Integration of multimodal data from a cohort of pancreatic ductal adenocarcinoma (PDAC) patients revealed expression of specific Alu repeats predicted to form double-stranded RNAs (dsRNAs) and trigger retinoic-acid-inducible gene I (RIG-I)-like-receptor (RLR)-associated type-I interferon (IFN) signaling. Such Alu-derived dsRNAs also anti-correlated with pro-tumorigenic macrophage infiltration in late stage tumors. We defined two complementary pathways whereby PDAC may adapt to such anti-tumorigenic signaling. In mutant TP53 tumors, ORF1p from long interspersed nuclear element (LINE)-1 preferentially binds Alus and decreases their expression, whereas adenosine deaminases acting on RNA 1 (ADAR1) editing primarily reduces dsRNA formation in wild-type TP53 tumors. Depletion of either LINE-1 ORF1p or ADAR1 reduced tumor growth in vitro. The fact that tumors utilize multiple pathways to mitigate immunostimulatory repeats implies the stress from their expression is a fundamental phenomenon to which PDAC, and likely other tumors, adapt.

Indexed as

Alu ElementsCarcinoma, Pancreatic DuctalLong Interspersed Nucleotide ElementsPancreatic NeoplasmsRNA-Binding ProteinsRNA, Double-StrandedTumor MicroenvironmentTumor Suppressor Protein p53Adenosine DeaminaseAnimalsCell Line, TumorGene Expression Regulation, NeoplasticHumansInterferon Type IMacrophagesMiceADAR protein, humanAdenosine DeaminaseInterferon Type IRetroelementsRNA-Binding ProteinsRNA, Double-StrandedTumor Suppressor Protein p53ADAR1cancer evolutioncancer immunityinverted AlusretrotransposonsTp53tumor-immune microenvironment

Identifiers

PMID39577413
PMCPMC12022969

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Registered trials

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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.