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  3. Red Blood Cells Internalize Extracellular DNA via Apoptotic Bodies with Clinical Relevance to Cancer Patients

Red Blood Cells Internalize Extracellular DNA via Apoptotic Bodies with Clinical Relevance to Cancer Patients

  • Adv Sci (Weinh). 2026 Mar;13(13):e11408. doi: 10.1002/advs.202511408.
Zihang Zeng 1,  Zongbi Yi 1,  Jing Hu 1,  Jiali Li 2,  Yu Xu 1,  Xiuli Guo 1,  Qian Ji 1,  Kaixiang Feng 1,  Ying Zhang 1,  Sirui Bai 1,  Yushuang Tan 1 3,  Yufei Yan 1 3,  Linzhi Han 1,  Jing Jiang 1,  Tengfei Wang 1,  Xiang Wang 1,  Ziqing Zhan 1,  Ruiying Huang 1,  Jinfang Zhang 1 4,  Conghua Xie 1 5,  Binghe Xu 1 4 6
Affiliations

Affiliations

  • 1 Department of Radiation and Medical Oncology, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Provincial Clinical Research Center For Cancer, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China.
  • 2 Department of Nuclear Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China.
  • 3 Tumor Precision Diagnosis and Treatment Technology and Translational Medicine, Hubei Engineering Research Center, Zhongnan Hospital of Wuhan University, Wuhan, China.
  • 4 Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China.
  • 5 Wuhan Research Center For Infectious Diseases and Cancer, Chinese Academy of Medical Sciences, Wuhan, China.
  • 6 State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
PMID: 41486873 DOI: 10.1002/advs.202511408
Abstract

Mature red blood cells (RBCs), the most abundant anucleate cells in humans, have long been overlooked as DNA carriers. Recent evidence implicates RBC-derived DNA (rbcDNA) as a potential biomarker for Cancer diagnostics, yet its origin and how RBCs acquire tumor DNA remain poorly understood. Here, we find that mature RBCs harbor short DNA fragments distinct from genomic DNA. Both in vivo and in vitro experiments confirm that RBCs can internalize extracellular DNA and reflect tumor burden. Oxford Nanopore Sequencing of rbcDNA reveals that short rbcDNA fragments are homologous to extracellular cell-free DNA (cfDNA). We identify apoptotic bodies (apoBDs) as key mediators of extracellular DNA uptake by RBCs, triggering RBC deformation, Heinz body formation, oxidative stress, and vesiculation. Tumor apoBD-treated RBCs are rapidly cleared in vivo via a partly macrophage-dependent effect, causing local immunosuppression in the spleen. Clinically, rbcDNA shows no advantage in detecting driver mutations compared with cfDNA, but its abundance significantly correlates with tumor burden and treatment response. Overall, our findings offer novel insights into RBC biology and support rbcDNA's clinical application in liquid biopsy.

Keywords

apoptotic bodies; cancers; genomics; liquid biopsy; red blood cells.

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