Serum inhibits the immunosuppressive function of myeloid-derived suppressor cells isolated from 4T1 tumor-bearing mice |
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Authors: | Melisa J Hamilton Judit P Banáth Vivian Lam Nancy E LePard Gerald Krystal Kevin L Bennewith |
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Institution: | (1) Terry Fox Laboratory, British Columbia Cancer Agency Research Centre, Vancouver, BC, Canada;(2) Department of Integrative Oncology, British Columbia Cancer Agency Research Centre, Vancouver, BC, Canada;(3) Department of Integrative Oncology, British Columbia Cancer Agency Research Centre, 675 West 10th Avenue, Room 9-107, Vancouver, BC, V5Z 1L3, Canada; |
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Abstract: | As more groups investigate the role of myeloid-derived suppressor cells (MDSCs) in promoting the growth of primary tumors
and distant tumor metastases, it is imperative to ensure the accurate detection and quantification of MDSC immunosuppression
ex vivo. MDSCs are defined by their ability to suppress immune responses. Although different in vitro culture conditions have
been used to study MDSCs, the effect of different culture conditions on MDSC immunosuppression is unknown. We therefore isolated
MDSCs from the lungs and spleens of 4T1 murine mammary tumor-bearing mice and assayed MDSC-mediated suppression of T cell
responses under different culture conditions. We found that 4T1-induced MDSCs effectively suppressed T cell proliferation
under serum-free conditions, but not when fetal calf serum (FCS) was present. FCS neither altered the immunosuppressive activities
of other myeloid cell types (i.e., peritoneal or tumor-associated macrophages) nor modified the susceptibility of T cells
to myeloid cell-mediated suppression, but instead acted directly on 4T1-induced MDSCs to significantly reduce their immunosuppressive
function. Importantly, we found that bovine serum albumin was a major contributor to the antagonistic effects of FCS on 4T1-induced
MDSC immunosuppression by inhibiting reactive oxygen species production from MDSCs. This work reveals that in vitro culture
conditions influence the immunosuppressive properties of MDSCs and highlights the importance of testing different culture
conditions on MDSC phenotype to ensure that MDSC immunosuppression is not being masked. These data have important implications
for the accurate detection and identification of MDSCs, as well as for determining the influence of MDSC-mediated immunosuppression
on primary and metastatic tumor growth. |
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