Table 1.

Molecular factors cancer-specifically driving self-renewal of macrophages.

Molecular Factor	Mechanism to Drive Macrophages Self-Renewal	References
CSF-1	• ERK1/2 activation, inducing the activation of Ets transcription factors, thus increasing of cyclin-D expression.	[12,78].
	• ERK5 activation, downregulation of p21 expression and increased expression of Ets2 and Cyclin-D	[63]
	• KLF2 and KLF4 upregulation.	[13]
	• c-myc upregulation.	[13]
IL-34	• Partially affects TAMs proliferation through its ability to interact with CSF1R.	[99]
GM-CSF	• Activation of JAK2/STAT5 pathway.	[12,13,14]
	• Activation of Bhlhe40/Bhlhe41 which inhibits c-Maf and Mafb transcription factors, thereby directly promoting expression of transcripts encoding cell cycle-related proteins.	[107,108]
ADO-1	• Working synergically with GM-CSF causes the upregulaion of PI3K/Akt and MEK/ERK signaling downstream of A2A activation.	[106]
	• Promotes macrophage proliferation, in part, through the transcriptional regulation of A2A.	[106]
IL-4	• Induce the transcription of STAT6 and activates PI3K/AKT signaling.	[12]
	• May stimulate macrophage proliferation in an Akt- and ACLY-dependent manner.	[109]