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Effect of tumor burden on myeloid derived suppressor cells and cytokine expression
Author(s) -
Talmadge James E.,
Dafferner Alicia,
Donkor Moses,
Westphal Sherry,
Younos Ibrahim,
Verma Vivek,
Hoke Traci,
Scholar Eric
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1078.25
Subject(s) - spleen , myeloid derived suppressor cell , myeloid , tumor necrosis factor alpha , parenchyma , cytokine , suppressor , clone (java method) , biology , cancer research , immunology , medicine , pathology , cancer , gene , biochemistry
Tumors growth has been suggested to suppress host immunity, including tumor infiltration by histocytes and T cells. We report herein that the frequency of myeloid derived suppressor cells (MDSCs) are significantly increased in the tumors, spleens, lungs and livers of mice bearing orthotopic clone‐66, mammary tumors in a tumor burden and duration dependant manner, while T cell numbers are suppressed. The increases in tumor burden and MDSC number are associated with significantly increased levels of VEGF‐a transcripts from tumor infiltrating myeloid cells (TIMCs), but not spleen cells or tumor parenchyma. Tumor burden and MDSC numbers are also directly correlated with G‐ and GM‐CSF transcript levels from the tumor parenchyma. In contrast, T cell numbers are inversely correlated with NOS‐2, ARG‐1 and COX‐2 transcript levels in the TIMCs, but not spleen cells, while MDSC numbers in the spleen and TIMCs are directly correlated with these enzyme transcript levels. These results suggest that the tumor associated increase in MDSC numbers was associated with G‐ and GM‐CSF and VEGF‐a secretion, while the activation of the MDSCs and secretion of ARG‐1 and NOS‐2 was associated with increased COX‐2 activity.