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Table 1 The regulatory function of estrogen and ER in cancer cell and various TME components

From: Estrogen/ER in anti-tumor immunity regulation to tumor cell and tumor microenvironment

TME Subtype Regulation Mechanism References
Cancer cells PD-L1 Down Decrease the PD-L1 transcription [62]
Inhibite the expression of PD-L1 by IL-17 pathway down-regulation [64]
Cause p-RB and c-Myc expression [67]
Enhance the poly-ubiquitination of PD-L1 by CSN5 in GPER-induced NF-κB pathway [35, 68]
Up Promote the post-transcriptional modification of PD-L1 [69]
Activate the ERK-induced PD-L1 expression (prediction) [70, 71]
CSCs Up Stabilize the DLL1-induced Notch signaling activation [78]
Mediate the elevated expression of FGF and EGF [79]
Down Inhibit the expression of CSCs marker by DNA methylation decrease [81]
T cells CTLs Down Alternate T cell maturity [82,83,84]
Up Activate the ERK and AKT phosphorylation, cell-specific Ca2+ signal, and NF-κB pathway [85]
Tregs Up Increase the differentiation of Treg [86,87,88]
Inhibit the function of APC [91]
Double-regulation Treg increase in high estrogen level and decrease in low estrogen level [58, 92]
TAMs M1 Down Cause the NOS2 repression and Arg1 increase [101]
M2 Up Deplete the mobilization of NF-κB and iNOS pathway by GPER1 [104]
CAFs Up Promote the expression of VEGF, CTGF, c-fos, Cyr61, EGR1, and FGFR1 [114,115,116]
Cytokines & chemokines Cytokines Double-regulation Increase IL-1β from cancer cells
Increase IL-4, IL-6, TNFα, and IL-17A from immunosuppressive cells
Decrease IL-12 and IFNγ from effector T cells
[123, 124]
Chemokines Up Promote the secretion of CCL2, CXCL11, and CXCL12 [125,126,127]
Collagen Up Manipulate by MAPK pathway and AP-1 (prediction) [128]
  1. TME Tumor Microenvironment, CSCs cancer stem cells, CTLs cytotoxic T lymphocytes, Tregs regulatory T cells, TAMs tumor-associated macrophages, CAFs cancer-associated fibroblasts