Evidence map›Paper›PMID 38281962›Full record

ArticleGenome medicine2024

Single-cell analysis of immune and stroma cell remodeling in clear cell renal cell carcinoma primary tumors and bone metastatic lesions.

Shenglin Mei, Adele M Alchahin, Ioanna Tsea, Youmna Kfoury, Taghreed Hirz, Nathan Elias Jeffries, Ting Zhao, Yanxin Xu, Hanyu Zhang, Hirak Sarkar and 14 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Genome medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
11.5field-weighted citation impact, top 1% 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

35 citing papers in PubMed, 48 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Article
  6. Article
  7. Review
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  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

24 authors at 3 institutions in 2 countries.

Shenglin Mei *Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA. smei8@mgh.harvard.edu.ORCID 0000-0001-8258-5898
Adele M Alchahin *Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, 17176, Stockholm, Sweden.
Ioanna Tsea *Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, 17176, Stockholm, Sweden.
Youmna KfouryCenter for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA.
Taghreed HirzCenter for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA.
Nathan Elias JeffriesCenter for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA.
Ting ZhaoCenter for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA.
Yanxin XuCenter for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA.
Hanyu ZhangCenter for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA.
Hirak SarkarDepartment of Biomedical Informatics, Harvard Medical School, Boston, MA, 02115, USA.
Shulin WuDepartment of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.
Alexander O SubtelnyDepartment of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.
John Inge JohnsenChildhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, 17176, Stockholm, Sweden.
Yida ZhangDepartment of Biomedical Informatics, Harvard Medical School, Boston, MA, 02115, USA.
Keyan SalariDepartment of Urology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.
Chin-Lee WuDepartment of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.
Mark A RandolphDivision of Plastic and Reconstructive Surgery, Massachusetts General Hospital, Boston, MA, 02114, USA.
David T ScaddenCenter for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA.
Douglas M DahlDepartment of Urology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.
John ShinDepartment of Neurosurgery, Harvard Medical School, Boston, MA, 02115, USA. shin.john@mgh.harvard.edu.
Peter V KharchenkoDepartment of Biomedical Informatics, Harvard Medical School, Boston, MA, 02115, USA. peter.kharchenko@gmail.com.
Philip J SaylorMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, 02114, USA. psaylor@mgh.harvard.edu.
David B SykesCenter for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA. dbsykes@mgh.harvard.edu.
Ninib BaryawnoChildhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, 17176, Stockholm, Sweden. n.baryawno@ki.se.
Harvard University · USKarolinska Institutet · SEMassachusetts General Hospital · US

Funding

Statistical methods for analysis of single-cell variabilityR01HL131768 · NHLBI · HARVARD MEDICAL SCHOOL · PI KHARCHENKO, PETER V · 2015 to 2019
$2.4M
NHLBI Division of Intramural Research NHLBINHLBI NIH HHS R01 HL131768prostate cancer foundation 23YOUN13Vetenskapsrådet Swedish Cancer SocietyVetenskapsrådet Swedish Research Council
6 · The paper itself

Abstract

backgroundDespite therapeutic advances, once a cancer has metastasized to the bone, it represents a highly morbid and lethal disease. One third of patients with advanced clear cell renal cell carcinoma (ccRCC) present with bone metastasis at the time of diagnosis. However, the bone metastatic niche in humans, including the immune and stromal microenvironments, has not been well-defined, hindering progress towards identification of therapeutic targets.

methodsWe collected fresh patient samples and performed single-cell transcriptomic profiling of solid metastatic tissue (Bone Met), liquid bone marrow at the vertebral level of spinal cord compression (Involved), and liquid bone marrow from a different vertebral body distant from the tumor site but within the surgical field (Distal), as well as bone marrow from patients undergoing hip replacement surgery (Benign). In addition, we incorporated single-cell data from primary ccRCC tumors (ccRCC Primary) for comparative analysis.

resultsThe bone marrow of metastatic patients is immune-suppressive, featuring increased, exhausted CD8 + cytotoxic T cells, T regulatory cells, and tumor-associated macrophages (TAM) with distinct transcriptional states in metastatic lesions. Bone marrow stroma from tumor samples demonstrated a tumor-associated mesenchymal stromal cell population (TA-MSC) that appears to be supportive of epithelial-to mesenchymal transition (EMT), bone remodeling, and a cancer-associated fibroblast (CAFs) phenotype. This stromal subset is associated with poor progression-free and overall survival and also markedly upregulates bone remodeling through the dysregulation of RANK/RANKL/OPG signaling activity in bone cells, ultimately leading to bone resorption.

conclusionsThese results provide a comprehensive analysis of the bone marrow niche in the setting of human metastatic cancer and highlight potential therapeutic targets for both cell populations and communication channels.

Indexed as

Carcinoma, Renal CellGene Expression ProfilingHumansSignal TransductionSingle-Cell AnalysisStromal CellsTumor Microenvironment

Identifiers

PMID38281962
PMCPMC10823713
OpenAlexW4391296762

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.