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Primary tumor-induced immunity eradicates disseminated tumor cells in syngeneic mouse model

Raziye Piranlioglu, EunMi Lee, Maria Ouzounova, Roni J. Bollag, Alicia H. Vinyard, Ali S. Arbab, Daniela Marasco, Mustafa Guzel, John K. Cowell, Muthushamy Thangaraju, Ahmed Chadli, Khaled A. Hassan, Max S. Wicha, Esteban Celis and Hasan Korkaya ()
Additional contact information
Raziye Piranlioglu: Augusta University
EunMi Lee: Augusta University
Maria Ouzounova: Cancer Research Center of Lyon
Roni J. Bollag: Augusta University
Alicia H. Vinyard: Augusta University
Ali S. Arbab: Augusta University
Daniela Marasco: University of Naples “Federico II”
Mustafa Guzel: Medipol University
John K. Cowell: Augusta University
Muthushamy Thangaraju: Augusta University
Ahmed Chadli: Augusta University
Khaled A. Hassan: University of Michigan
Max S. Wicha: University of Michigan
Esteban Celis: Augusta University
Hasan Korkaya: Augusta University

Nature Communications, 2019, vol. 10, issue 1, 1-13

Abstract: Abstract Although clinically apparent metastasis is associated with late stages of cancer development, micro-metastatic dissemination may be an early event. However, the fate of these early disseminated tumor cells (DTC) remains elusive. We show that despite their capacity to disseminate into secondary organs, 4T1 tumor models develop overt metastasis while EMT6-tumor bearing mice clear DTCs shed from primary tumors as well as those introduced by intravenous (IV) injection. Following the surgical resection of primary EMT6 tumors, mice do not develop detectable metastasis and reject IV-injected tumor cells. In contrast, these cells readily grow and metastasize in immuno-deficient athymic or Rag2−/− mice, an effect mimicked by CD8+ T-cell depletion in immunocompetent mice. Furthermore, recombinant G-CSF or adoptive transfer of granulocytic-MDSCs isolated from 4T1 tumor-bearing mice, induce metastasis by suppressing CD8+ T-cells in EMT6-primed mice. Our studies support the concept of immune surveillance providing molecular insights into the immune mechanisms during tumor progression.

Date: 2019
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09015-1

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DOI: 10.1038/s41467-019-09015-1

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