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

Raziye Piranlioglu, Eun Mi Lee, Maria Ouzounova, Roni Jacob Bollag, Alicia Vinyard, Ali Syed Arbab, Daniela Marasco, Mustafa Guzel, John Kenneth Cowell, Muthusamy Thangaraju, Ahmed Chadli, Khaled A. Hassan, Max S. Wicha, Esteban Celis, Hasan Korkaya

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number1430
JournalNature Communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

Fingerprint

immunity
mice
Tumors
Immunity
tumors
Cells
metastasis
Neoplasms
Bearings (structural)
Neoplasm Metastasis
T-cells
sheds
T-Lymphocytes
Granulocyte Colony-Stimulating Factor
Adoptive Transfer
surveillance
progressions
organs
Intravenous Injections
depletion

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Primary tumor-induced immunity eradicates disseminated tumor cells in syngeneic mouse model. / Piranlioglu, Raziye; Lee, Eun Mi; Ouzounova, Maria; Bollag, Roni Jacob; Vinyard, Alicia; Arbab, Ali Syed; Marasco, Daniela; Guzel, Mustafa; Cowell, John Kenneth; Thangaraju, Muthusamy; Chadli, Ahmed; Hassan, Khaled A.; Wicha, Max S.; Celis, Esteban; Korkaya, Hasan.

In: Nature Communications, Vol. 10, No. 1, 1430, 01.12.2019.

Research output: Contribution to journalArticle

@article{8c4976a404d84c0dba17fdd065b8f64a,
title = "Primary tumor-induced immunity eradicates disseminated tumor cells in syngeneic mouse model",
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.",
author = "Raziye Piranlioglu and Lee, {Eun Mi} and Maria Ouzounova and Bollag, {Roni Jacob} and Alicia Vinyard and Arbab, {Ali Syed} and Daniela Marasco and Mustafa Guzel and Cowell, {John Kenneth} and Muthusamy Thangaraju and Ahmed Chadli and Hassan, {Khaled A.} and Wicha, {Max S.} and Esteban Celis and Hasan Korkaya",
year = "2019",
month = "12",
day = "1",
doi = "10.1038/s41467-019-09015-1",
language = "English (US)",
volume = "10",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Primary tumor-induced immunity eradicates disseminated tumor cells in syngeneic mouse model

AU - Piranlioglu, Raziye

AU - Lee, Eun Mi

AU - Ouzounova, Maria

AU - Bollag, Roni Jacob

AU - Vinyard, Alicia

AU - Arbab, Ali Syed

AU - Marasco, Daniela

AU - Guzel, Mustafa

AU - Cowell, John Kenneth

AU - Thangaraju, Muthusamy

AU - Chadli, Ahmed

AU - Hassan, Khaled A.

AU - Wicha, Max S.

AU - Celis, Esteban

AU - Korkaya, Hasan

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85063734457&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85063734457&partnerID=8YFLogxK

U2 - 10.1038/s41467-019-09015-1

DO - 10.1038/s41467-019-09015-1

M3 - Article

VL - 10

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 1430

ER -