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CD11b(+)/Gr-1(+) immature myeloid cells mediate suppression of T cells in mice bearing tumors of IL-1 beta-secreting cells

Song, X P; Krelin, Y; Dvorkin, T; Björkdahl, Olle LU ; Segal, S; Dinarello, C A; Voronov, E and Apte, R N (2005) In Journal of Immunology 175(12). p.8200-8208
Abstract
Tumor cells secreting IL-1 beta are invasive and metastatic, more than the parental line or control mock-transfected cells, and concomitantly induce in mice general immune suppression of T cell responses. Suppression strongly correlates with accumulation in the peripheral blood and spleen of CD11b(+)/Gr-1(+) immature myeloid cells and hematological alterations, such as splenomegaly, leukocytosis, and anemia. Resection of large tumors of IL-1 beta-secreting cells restored immune reactivity and hematological alterations within 7-10 days. Treatment of tumor-bearing mice with the physiological inhibitor of IL-1, the IL-1R antagonist, reduced tumor growth and attenuated the hematological alterations. Depletion of CD11b(+)/Gr-1(+) immature... (More)
Tumor cells secreting IL-1 beta are invasive and metastatic, more than the parental line or control mock-transfected cells, and concomitantly induce in mice general immune suppression of T cell responses. Suppression strongly correlates with accumulation in the peripheral blood and spleen of CD11b(+)/Gr-1(+) immature myeloid cells and hematological alterations, such as splenomegaly, leukocytosis, and anemia. Resection of large tumors of IL-1 beta-secreting cells restored immune reactivity and hematological alterations within 7-10 days. Treatment of tumor-bearing mice with the physiological inhibitor of IL-1, the IL-1R antagonist, reduced tumor growth and attenuated the hematological alterations. Depletion of CD11b(+)/Gr-1(+) immature myeloid cells from splenocytes of tumor-bearing mice abrogated suppression. Despite tumor-mediated suppression, resection of large tumors of IL-1 beta-secreting cells, followed by a challenge with the wild-type parental cells, induced resistance in mice; protection was not observed in mice bearing tumors of mock-transfected fibrosarcoma cells. Altogether, we show in this study that tumor-derived IL-1 beta, in addition to its proinflammatory effects on tumor invasiveness, induces in the host hematological alterations and tumor-mediated suppression. Furthermore, the antitumor effectiveness of the IL-1R antagonist was also shown to encompass restoration of hematological alterations, in addition to its favorable effects on tumor invasiveness and angiogenesis that have previously been described by us. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Immunology
volume
175
issue
12
pages
8200 - 8208
publisher
American Association of Immunologists
external identifiers
  • pmid:16339559
  • wos:000234030400050
ISSN
1550-6606
language
English
LU publication?
yes
id
77ef66f8-4c8d-47c2-aef1-bc31f84e5f56 (old id 210741)
alternative location
http://www.jimmunol.org/cgi/content/abstract/175/12/8200
date added to LUP
2007-08-08 09:18:28
date last changed
2016-04-16 04:16:00
@article{77ef66f8-4c8d-47c2-aef1-bc31f84e5f56,
  abstract     = {Tumor cells secreting IL-1 beta are invasive and metastatic, more than the parental line or control mock-transfected cells, and concomitantly induce in mice general immune suppression of T cell responses. Suppression strongly correlates with accumulation in the peripheral blood and spleen of CD11b(+)/Gr-1(+) immature myeloid cells and hematological alterations, such as splenomegaly, leukocytosis, and anemia. Resection of large tumors of IL-1 beta-secreting cells restored immune reactivity and hematological alterations within 7-10 days. Treatment of tumor-bearing mice with the physiological inhibitor of IL-1, the IL-1R antagonist, reduced tumor growth and attenuated the hematological alterations. Depletion of CD11b(+)/Gr-1(+) immature myeloid cells from splenocytes of tumor-bearing mice abrogated suppression. Despite tumor-mediated suppression, resection of large tumors of IL-1 beta-secreting cells, followed by a challenge with the wild-type parental cells, induced resistance in mice; protection was not observed in mice bearing tumors of mock-transfected fibrosarcoma cells. Altogether, we show in this study that tumor-derived IL-1 beta, in addition to its proinflammatory effects on tumor invasiveness, induces in the host hematological alterations and tumor-mediated suppression. Furthermore, the antitumor effectiveness of the IL-1R antagonist was also shown to encompass restoration of hematological alterations, in addition to its favorable effects on tumor invasiveness and angiogenesis that have previously been described by us.},
  author       = {Song, X P and Krelin, Y and Dvorkin, T and Björkdahl, Olle and Segal, S and Dinarello, C A and Voronov, E and Apte, R N},
  issn         = {1550-6606},
  language     = {eng},
  number       = {12},
  pages        = {8200--8208},
  publisher    = {American Association of Immunologists},
  series       = {Journal of Immunology},
  title        = {CD11b(+)/Gr-1(+) immature myeloid cells mediate suppression of T cells in mice bearing tumors of IL-1 beta-secreting cells},
  volume       = {175},
  year         = {2005},
}