---
title: "Platelet-programmed circulating tumor cells engage monocytes via a candidate CD40LG–ITGA5:ITGB1 my"
id: "biorxiv-7-platelet-programmed-circulating-tumor-cells-signal-to-monocytes-through-a"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-7-platelet-programmed-circulating-tumor-cells-signal-to-monocytes-through-a"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.09.20.752972v1?rss=1"
published_at: "2026-09-22T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Platelet-programmed circulating tumor cells engage monocytes via a candidate CD40LG–ITGA5:ITGB1 my
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-7-platelet-programmed-circulating-tumor-cells-signal-to-monocytes-through-a
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.09.20.752972v1?rss=1)
- **Published At:** 2026-09-22T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- Study integrates single-cell RNA-seq of **377 circulating tumor cells (CTCs)** and **2,634 white blood cells** to identify CTC subpopulations with platelet-like features. - Trajectory analysis defined a subset termed **Platelet-Programmed CTCs**, enriched for platelet aggregation functions and predicted resistance to NK cell cytotoxicity. - The authors estimated the platelet-programmed tumor cell proportion across **1,102 bulk RNA-seq** primary breast tumor samples using a Dampened Weighted Least Squares approach. - A higher platelet-programmed tumor cell proportion was strongly inversely associated with overall survival (Cox-PH p = 0.00419; HR = 6 per 10% increase; 95% CI: 1.76–20.7). - The survival association did not differ significantly between early- and late-stage patients according to the report. - Cell–cell communication analysis and molecular docking nominated the **CD40LG–ITGA5:ITGB1** ligand–receptor pair as a candidate **myeloid checkpoint** between platelet-programmed CTCs and monocytes (Hex docking score = −656.83; TNFα–TNFR reference = −515). - The study highlights a potential mechanism by which acquisition of platelet traits by CTCs could contribute to immune evasion and worse clinical outcomes in breast cancer. - Authors emphasize that experimental and clinical validation of the CD40LG–ITGA5:ITGB1 axis is required before translational application.
## Clinical Analysis & Structured Key Points
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Samane Khoshbakht 1 Icahn School of Medicine at Mount Sinai; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Samane%2BKhoshbakht%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Khoshbakht%20S&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ASamane%2BKhoshbakht%2B) * [ORCID record for Samane Khoshbakht](http://orcid.org/0000-0003-3253-7577 "Open in new tab") Hojat Borna 2 University of Tehran; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Hojat%2BBorna%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Borna%20H&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AHojat%2BBorna%2B) Mehrnaz Zarei 3 Duke University Department of Biology; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Mehrnaz%2BZarei%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Zarei%20M&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AMehrnaz%2BZarei%2B) Zahra Salehi 4 Tehran University of Medical Sciences; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Zahra%2BSalehi%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Salehi%20Z&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AZahra%2BSalehi%2B) Niloofar Hejazifar 5 University of Milan; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Niloofar%2BHejazifar%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Hejazifar%20N&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ANiloofar%2BHejazifar%2B) * [ORCID record for Niloofar Hejazifar](http://orcid.org/0009-0004-8628-2148 "Open in new tab") Yasaman Setayeshpour 6 Duke University; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Yasaman%2BSetayeshpour%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Setayeshpour%20Y&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AYasaman%2BSetayeshpour%2B) * [ORCID record for Yasaman Setayeshpour](http://orcid.org/0000-0002-3420-8841 "Open in new tab") Niroshana Anandasabapathy 7 Weill Cornell Medical College * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Niroshana%2BAnandasabapathy%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Anandasabapathy%20N&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ANiroshana%2BAnandasabapathy%2B) * [ORCID record for Niroshana Anandasabapathy](http://orcid.org/0000-0002-0473-8358 "Open in new tab") Mayte Suarez-Farinas 1 Icahn School of Medicine at Mount Sinai; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Mayte%2BSuarez-Farinas%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Suarez-Farinas%20M&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AMayte%2BSuarez-Farinas%2B) * For correspondence: mayte.suarezfarinas@mssm.edu * [Abstract](https://www.biorxiv.org/content/10.64898/2026.09.20.752972v1)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_art/node:5800664/1) * [Info/History](https://www.biorxiv.org/content/10.64898/2026.09.20.752972v1.article-info)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_info/node:5800664/1) * [Metrics](https://www.biorxiv.org/content/10.64898/2026.09.20.752972v1.article-metrics)[](https://www.biorxiv.org/panels_ajax_tab/article_tab_metrics/node:5800664/1) * [Supplementary material](https://www.biorxiv.org/content/10.64898/2026.09.20.752972v1.supplementary-material)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_data/node:5800664/1) * [ Preview PDF](https://www.biorxiv.org/content/10.64898/2026.09.20.752972v1.full.pdf+html)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_pdf/node:5800664/1) ![Loading](https://www.biorxiv.org/sites/all/modules/contrib/panels_ajax_tab/images/loading.gif) ## Abstract Circulating tumor cells (CTCs) are key drivers of distant metastasis, while platelets facilitate this process by protecting them from immune surveillance. However, the detection of CTCs exhibiting platelet markers and their communication with monocytes has not been thoroughly investigated. This study seeks to identify the intercellular communication of CTCs that have acquired platelet traits by integrating single-cell RNA-seq data of 377 CTCs and 2,634 white blood cells. Trajectory analysis identified a subpopulation of CTCs with enhanced platelet-related functions, including platelet aggregation and resistance to NK cell-mediated cytotoxicity, termed Platelet-Programmed CTCs. The Dampened Weighted Least Squares method was implemented to estimate the platelet-programmed tumor cell proportion in 1,102 bulk RNA-seq samples from primary breast cancer tumors. A strong inverse association was found between platelet-programmed tumor cell proportion and overall survival (Cox-PH p-value =0.00419, HR=6 per 10% increase in proportion, 95% CI:1.76-20.7). However, this association did not differ significantly between early- and late-stage patients. Cell-cell communication analyses and molecular docking revealed the CD40LG-ITGA5:ITGB1 pair as a potential immune checkpoint candidate for monocytes in cancer (Hex score=-656.83; TNFα-TNFR reference complex=-515). However, further experimental and clinical validation is required to translate these findings. In conclusion, these findings deepen our understanding of the immune evasion mechanisms of CTCs by acquiring platelet characteristics. This immune checkpoint axis offers a novel avenue for further experimental validation and future intervention. ### Competing Interest Statement The authors have declared no competing interest. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a [CC-BY-NC-ND 4.0 International license](http://creativecommons.org/licenses/by-nc-nd/4.0/). bioRxiv and medRxiv thank the following for their generous financial support: > The Chan Zuckerberg Initiative, Cold Spring Harbor Laboratory, the Sergey Brin Family Foundation, California Institute of Technology, Centre National de la Recherche Scientifique, Fred Hutchinson Cancer Center, Imperial College London, Massachusetts Institute of Technology, Stanford University, The University of Edinburgh, University of Washington, and Vrije Universiteit Amsterdam. [Donate to openRxiv ](https://www.zeffy.com/en-US/donation-form/donate-to-make-a-difference-10981) [ Back to top](https://www.biorxiv.org/content/10.64898/2026.09.20.752972v1?rss=1#page) [ Previous](https://www.biorxiv.org/content/10.1101/2025.09.30.679600v2 "Expansion of DNA-Encoded Library Hits Using Generative Chemistry and Ultra-Large Compound Catalogs")[Next ](https://www.biorxiv.org/content/10.64898/2026.04.27.720978v4 "Distinct Hippocampal Cellular Pathologies Influence Cognition Across Diagnostic Categories, Also Distinguishing Schizophrenia from Affective Psychoses") Posted September 22, 2026. [ Download PDF](https://www.biorxiv.org/content/10.64898/2026.09.20.752972v1.full.pdf) Print/Save Options [Download PDF](https://www.biorxiv.org/content/biorxiv/early/2026/09/22/2026.09.20.752972.full.pdf)Full Text & In-line FiguresXML [More Info](https://www.biorxiv.org/about/FAQ#PrintOptions "More Information on Print/Save Options") [Supplementary Material ](https://www.biorxiv.org/content/10.64898/2026.09.20.752972v1.supplementary-material) [ Email](https://www.biorxiv.org/ "Email this Article") [ Share](https://www.biorxiv.org/) Platelet-programmed circulating tumor cells signal to monocytes through a candidate CD40LG-ITGA5:ITGB1 myeloid checkpoint axis in breast cancer Samane Khoshbakht, Hojat Borna, Mehrnaz Zarei, Zahra Salehi, Niloofar Hejazifar, Yasaman Setayeshpour, Niroshana Anandasabapathy, Mayte Suarez-Farinas bioRxiv 2026.09.20.752972; doi: https://doi.org/10.64898/2026.09.20.752972 This article is a preprint and has not been certified by peer review [[what does this mean?](https://www.biorxiv.org/about/FAQ#unrefereed)]. 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