Evidence map›Paper›PMID 40707771›Full record

ArticleCommunications medicine2025

Simultaneous expression of epithelial and immune cell markers in circulating tumor cells identified in patients with stage 4 breast cancer.

Nikki Higa, Audrey Limb, Valerie Hennes, Andrés Rivera, Rafael Nevarez, Anand Kolatkar, Carol K Tweed, Adam I Riker, Young Lee, Lorraine Tafra and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Communications medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

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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

14 authors.

Nikki HigaConvergent Science Institute in Cancer, Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA, 90089, USA.ORCID http://orcid.org/0000-0003-3236-8929
Audrey LimbConvergent Science Institute in Cancer, Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA, 90089, USA.
Valerie HennesConvergent Science Institute in Cancer, Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA, 90089, USA.
Andrés RiveraConvergent Science Institute in Cancer, Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA, 90089, USA.
Rafael NevarezConvergent Science Institute in Cancer, Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA, 90089, USA.
Anand KolatkarConvergent Science Institute in Cancer, Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA, 90089, USA.ORCID http://orcid.org/0000-0002-8621-1073
Carol K TweedLuminis Health, Anne Arundel Medical Center, DeCesaris Cancer Institute, Annapolis, MD, 21401, USA.
Adam I RikerLuminis Health, Anne Arundel Medical Center, DeCesaris Cancer Institute, Annapolis, MD, 21401, USA.
Young LeeLuminis Health, Anne Arundel Medical Center, DeCesaris Cancer Institute, Annapolis, MD, 21401, USA.
Lorraine TafraLuminis Health, Anne Arundel Medical Center, DeCesaris Cancer Institute, Annapolis, MD, 21401, USA.
Jeremy G PerkinsMurtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD, 20889, USA.
Craig D ShriverMurtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD, 20889, USA.ORCID http://orcid.org/0000-0001-8993-5811
Peter KuhnConvergent Science Institute in Cancer, Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA, 90089, USA. pkuhn@usc.edu.
James HicksConvergent Science Institute in Cancer, Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA, 90089, USA. jameshic@usc.edu.ORCID http://orcid.org/0000-0001-5353-4338

Funding

USC/NORRIS COMPREHENSIVE CANCER CENTER (CORE) SUPPORTP30CA014089 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Fumito Ito · 1985 to 2026
$181.4M
Breast Cancer Research Foundation (BCRF) BCRF-16-189Breast Cancer Research Foundation (BCRF) BCRF-18-089NCI NIH HHS P30 CA014089U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) 5P30CA014089-40
6 · The paper itself

Abstract

backgroundHeterogeneous circulating tumor cells (CTCs) have been implicated in the formation of new metastases. However, circulating cells expressing both tumor and immune cell proteins are often dismissed as insignificant findings in CTC studies.

methodsTwo non-contemporaneous blood samples from a metastatic breast cancer patient were analyzed using an enrichment-free platform to identify canonical, epithelial-only CTCs (CD45-/cytokeratin + , epi.CTCs) and CD45 + /cytokeratin+ immune-like CTCs (im.CTCs). Single cells from both samples were subjected to copy number and protein expression profiling. A cohort of 36 metastatic breast cancer patients was then analyzed to search for additional cases with im.CTCs.

resultsHere, we identified and characterized a population of CTCs exhibiting an immune-like state. In two samples from an index patient, im.CTCs outnumbered epi.CTCs, comprising >97% of the CTC population. Single-cell copy number analysis of 43 im.CTCs and 30 epi.CTCs revealed clonal alterations across both populations, confirming a shared tumor origin. Furthermore, im.CTCs contained pseudo-diploid profiles that did not reflect dilution from the addition of a normal diploid genome, indicating that they were unlikely to have originated from tumor-immune cell fusion. Protein expression analysis showed that im.CTCs express CD45 as well as other immune-related markers, such as CD3 and CD4, and the cancer stemness marker, CD44. Subsequent analysis of a metastatic breast cancer cohort identified an additional patient harboring im.CTCs with the same tumor-derived, non-fusion genome as in the index case.

conclusionsCollectively, these genomic and proteomic features distinguish im.CTCs from previously reported circulating cells may represent a novel form of tumor cell plasticity.

Identifiers

PMID40707771
PMCPMC12290075

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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.