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

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]