TY - JOUR
T1 - Cancer Cells Promote Immune Regulatory Function of Macrophages by Upregulating Scavenger Receptor MARCO Expression
AU - Gu, Chao
AU - Wiest, Matthew
AU - Zhang, Wei
AU - Halder, Kuntal
AU - Zurawski, Sandy
AU - Zurawski, Gerard
AU - Joo, Hye Mee
AU - Oh, Sang Kon
N1 - Publisher Copyright:
Copyright © 2023 by The American Association of Immunologists, Inc.
PY - 2023/7/1
Y1 - 2023/7/1
N2 - Expression of macrophage receptor with collagenous structure (MARCO) by tumor-associated macrophages is associated with poor prognosis of multiple types of cancer. In this article, we report that cancer cells (e.g., breast cancer and glioblastoma cell lines) can upregulate surface MARCO expression on human macrophages not only via IL-6-induced STAT3 activation but also via sphingosine-1phosphate receptor (S1PR)-mediated IL-6 and IL-10 expression followed by STAT3 activation. We further found that MARCO ligation induces activation of the MEK/ERK/p90RSK/CREB signaling cascade, leading to IL-10 expression followed by STAT3-dependent PDL1 upregulation. Such MARCO-induced macrophage polarization is accompanied by increased expression of PPARG, IRF4, IDO1, CCL17, and CCL22. Ligation of surface MARCO can thus result in decreased T cell responses mainly by reduction of their proliferation. Taken together, cancer cell-induced MARCO expression and its intrinsic regulatory function within macrophages are, to our knowledge, new aspects of cancer immune evasion mechanisms that need to be further studied in the future.
AB - Expression of macrophage receptor with collagenous structure (MARCO) by tumor-associated macrophages is associated with poor prognosis of multiple types of cancer. In this article, we report that cancer cells (e.g., breast cancer and glioblastoma cell lines) can upregulate surface MARCO expression on human macrophages not only via IL-6-induced STAT3 activation but also via sphingosine-1phosphate receptor (S1PR)-mediated IL-6 and IL-10 expression followed by STAT3 activation. We further found that MARCO ligation induces activation of the MEK/ERK/p90RSK/CREB signaling cascade, leading to IL-10 expression followed by STAT3-dependent PDL1 upregulation. Such MARCO-induced macrophage polarization is accompanied by increased expression of PPARG, IRF4, IDO1, CCL17, and CCL22. Ligation of surface MARCO can thus result in decreased T cell responses mainly by reduction of their proliferation. Taken together, cancer cell-induced MARCO expression and its intrinsic regulatory function within macrophages are, to our knowledge, new aspects of cancer immune evasion mechanisms that need to be further studied in the future.
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U2 - 10.4049/jimmunol.2300029
DO - 10.4049/jimmunol.2300029
M3 - Article
C2 - 37212598
AN - SCOPUS:85163922086
SN - 0022-1767
VL - 211
SP - 57
EP - 70
JO - Journal of Immunology
JF - Journal of Immunology
IS - 1
ER -