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
N1 - Publisher Copyright:
© 2019, The Author(s).
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
C2 - 30926774
AN - SCOPUS:85063734457
SN - 2041-1723
VL - 10
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 1430
ER -