Evidence map›Paper›PMID 39386723›Full record

ArticlebioRxiv : the preprint server for biology2024

Multimodal Spatial Profiling Reveals Immune Suppression and Microenvironment Remodeling in Fallopian Tube Precursors to High-Grade Serous Ovarian Carcinoma.

Tanjina Kader, Jia-Ren Lin, Clemens Hug, Shannon Coy, Yu-An Chen, Ino de Bruijn, Natalie Shih, Euihye Jung, Roxanne J Pelletier, Mariana Lopez Leon and 19 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. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

29 authors.

Tanjina KaderLaboratory of Systems Pharmacology, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-1463-7593
Jia-Ren LinLaboratory of Systems Pharmacology, Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-4702-7705
Clemens HugLaboratory of Systems Pharmacology, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-8299-3274
Shannon CoyLaboratory of Systems Pharmacology, Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-0033-9031
Yu-An ChenLaboratory of Systems Pharmacology, Harvard Medical School, Boston, MA, USA.ORCID 000-0001-7228-4696
Ino de BruijnMemorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065, USA.ORCID 0000-0001-5427-4750
Natalie ShihPenn Ovarian Cancer Research Center, Department of Obstetrics and Gynecology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.ORCID 0009-0007-5025-1026
Euihye JungPenn Ovarian Cancer Research Center, Department of Obstetrics and Gynecology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.ORCID 0000-0003-1202-247X
Roxanne J PelletierLaboratory of Systems Pharmacology, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-1957-5483
Mariana Lopez LeonLaboratory of Systems Pharmacology, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-4599-7719
Gabriel MingoPenn Ovarian Cancer Research Center, Department of Obstetrics and Gynecology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.ORCID 0000-0002-7593-5885
Dalia Khaled OmranPenn Ovarian Cancer Research Center, Department of Obstetrics and Gynecology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.ORCID 0000-0003-4323-2621
Jong Suk LeeLaboratory of Systems Pharmacology, Harvard Medical School, Boston, MA, USA.ORCID 0009-0008-4460-7118
Clarence YappLaboratory of Systems Pharmacology, Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-1144-5710
Baby Anusha SatravadaMemorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065, USA.ORCID 0000-0001-6608-345X
Ritika KundraMemorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065, USA.ORCID 0000-0001-6723-2859
Yilin XuLaboratory of Systems Pharmacology, Harvard Medical School, Boston, MA, USA.ORCID 0009-0002-5696-7475
Sabrina ChanLaboratory of Systems Pharmacology, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-4557-2972
Juliann B TefftLaboratory of Systems Pharmacology, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-8826-665X
Jeremy MuhlichLaboratory of Systems Pharmacology, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-0811-637X
Sarah KimPenn Ovarian Cancer Research Center, Department of Obstetrics and Gynecology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.ORCID 0000-0003-1381-6781
Stefan M GyslerPenn Ovarian Cancer Research Center, Department of Obstetrics and Gynecology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.ORCID 0000-0001-6188-8523
Judith AgudoDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID 0000-0002-3576-3169
James R HeathInstitute of Systems Biology, Seattle, WA, USA.
Nikolaus SchultzMemorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065, USA.ORCID 0000-0002-0131-4904
Charles DrescherSwedish Cancer Institute Gynecologic Oncology and Pelvic Surgery, Seattle, WA, USA.ORCID 0000-0002-6579-0416
Peter K SorgerLaboratory of Systems Pharmacology, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-3364-1838
Ronny DrapkinPenn Ovarian Cancer Research Center, Department of Obstetrics and Gynecology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.ORCID 0000-0002-6912-6977
Sandro SantagataLaboratory of Systems Pharmacology, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-7528-9668

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4M
SPORE in Ovarian CancerP50CA228991 · NCI · JOHNS HOPKINS UNIVERSITY · PI Amanda Nickles Fader · 2018 to 2026
$20.5M
Pre-cancer atlases of cutaneous and hematologic origin (PATCH Center)U2CCA233262 · NCI · HARVARD MEDICAL SCHOOL · PI SANTAGATA, SANDRO · 2018 to 2023
$8.7M
Advancing technologies for the collection and analysis of high dimensional immunoprofiles and tumor imagesR50CA274277 · NCI · HARVARD MEDICAL SCHOOL · PI Jia-Ren Lin · 2022 to 2026
$879k
NCI NIH HHS P30 CA008748NCI NIH HHS P50 CA228991NCI NIH HHS R50 CA274277NCI NIH HHS U2C CA233262
6 · The paper itself

Abstract

High-Grade Serous Ovarian Cancer (HGSOC) originates from fallopian tube (FT) precursors. However, the molecular changes that occur as precancerous lesions progress to HGSOC are not well understood. To address this, we integrated high-plex imaging and spatial transcriptomics to analyze human tissue samples at different stages of HGSOC development, including p53 signatures, serous tubal intraepithelial carcinomas (STIC), and invasive HGSOC. Our findings reveal immune modulating mechanisms within precursor epithelium, characterized by chromosomal instability, persistent interferon (IFN) signaling, and dysregulated innate and adaptive immunity. FT precursors display elevated expression of MHC-class I, including HLA-E, and IFN-stimulated genes, typically linked to later-stage tumorigenesis. These molecular alterations coincide with progressive shifts in the tumor microenvironment, transitioning from immune surveillance in early STICs to immune suppression in advanced STICs and cancer. These insights identify potential biomarkers and therapeutic targets for HGSOC interception and clarify the molecular transitions from precancer to cancer.

Indexed as

antigen presentationcancer progressionfallopian tubeHigh Grade Serous Ovarian CarcinomaHLA-AHLA-Ehomologous recombinant deficient tumorinnate immune systemmulti-plex imagingNatural Killer cellsOvarian cancerp53 signaturespreneoplasiaSerous Tubal Intraepithelial Carcinomasingle cellspatial transcriptomicstumor immune interactiontumor microenvironment

Identifiers

PMID39386723
PMCPMC11463462

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.