Table 2.

Cancer cell modulation of the TME.

Study	Cell Line	Factors	Impact	Reference
Mouse models
In vivo mouse model	MB49	IL10	Impairs dendritic cell activation and maturation Dampens activation of cytotoxic T-cells	[9]
In vitro allograft	MB49	CCL2	Induces M2 polarisation of tumor-associated macrophages (TAMs)	[10]
In vivo mouse model	-	Pyruvate kinase M2 (PKM2) controlled vascular endothelial growth factor (VEGF)	Increased angiogenesis	[8]
In vivo mouse model	MBT-2	Prostaglandin E 2 (PGE2)/cyclooxygenase 2 (COX2)	Increased expression of PD-L1 on macrophages and myeloid-derived suppressor cells (MDSC)	[14]
Human cell lines and cancer databases
In vitro assays (Boyden Chamber)	RT112, Cal-29	IL-8, IL-1	Recruit fibroblasts to the TME Paracrine signaling with fibroblasts, which promotes cancer invasion and migration	[12]
In vitro assay	T24	IL-1 and IL-1α	Endothelial activation Formation of leaky tumor vasculature	[4]
In vitro assay	Various Cell Lines	BMP4 secretion	Induces differentiation of M2 macrophages	[11]
In vitro and microfluidic assays	RT4, RT112, and T24/83	VEGF-A, IL-8, TIMP1	Endothelial activation	[5]
Human Database	The Cancer Genome Atlas (TCGA)	CCL4	Impaired T-cell activation due to decreased recruitment of DCs	[16]
In vitro assay	Patient derived Cell line	VEGF, cylin dependant kinase 4 (CDK4)	Increased migration and metastasis Increased angiogenesis	[6]
In vitro (transwell) assays	T24 253J	VEGF, CXC motif chemokine ligand 1 (CXCL1), CXCL5, CXCL8	Recruitment of endothelial cells (angiogenesis) Endothelial activation	[17]
In vitro assays	HT-1376, T24,5637(HTB-9), and J82	LINC00482	Increased inflammation (increased levels of IL-6, TNF, and IL-1β) Increased angiogenesis (VEGF)	[7]
3D cell culture and in vitro assays	J82, UMUC3, T24	CXCL1	Recruitment and activation of tumor-associated macrophages and cancer-associated fibroblasts	[13]
In vitro assays	T24 and UMUC3	Brain-derived neurotrophic factor (BDNF)	Paracrine signaling to BC cells Increased proliferation and invasion of BC cells	[18]