TABLE 1.

A list of the most prominent bioactive molecules in tumor microenvironment and their effect on phenotype of NK cells and tumor cells undergoing epithelial to mesenchymal transition (* Regular fonts indicate inhibition of NK antitumor activity whereas italics indicate activation).

Protein	Cell	Effect*	References
TGF-β	Tumor	MHC I downregulation	Chen et al., 2015; Lorenzo-Herrero et al., 2018; Fedele and Melisi, 2020
		E-cadherin downregulation	Thuault et al., 2006, 2008; López-Soto et al., 2013; Chockley et al., 2018
		MICA/B, ULBP1 upregulation	López-Soto et al., 2006, 2013; Bedel et al., 2011; Huergo-Zapico et al., 2014
	NK	NKG2D, NCR, DNAM1 downregulation	Zhang et al., 2012; Rocca et al., 2013, 2016; Schiavoni et al., 2013; Konjević et al., 2019; Ferretti et al., 2020
IL-6	Tumor	PDL-1 upregulation	Wang H. B. et al., 2017
IL-8	Tumor	E cadherin downregulation	Li et al., 2012; Palena et al., 2012
IL-10	Tumor	MHC I downregulation	Stanilov et al., 2010; Konjević et al., 2019
	NK	NKG2D, NCRs downregulation	Schiavoni et al., 2013; Konjević et al., 2016
TNF	Tumor	MICA downregulation	Bedel et al., 2011; De Simone et al., 2015
NO	NK	CD16 downregulation	Stiff et al., 2018
L-kynurenine	NK	NKG2D, NCR downregulation	Della Chiesa et al., 2006; Konjević et al., 2016
Prostaglandine E2	NK	NKG2D, NCR downregulation	Harizi, 2013; Park et al., 2018
VEGF	Tumor	E cadherin downregulation	Yang et al., 2006; Bendardaf et al., 2019
	NK	NKG2D downregulation	Bruno et al., 2018
EGF	Tumor	MHC I, E-cadherin downregulation	Chen et al., 2015
lactate	NK	NKp46 downregulation	Husain et al., 2013
Matrix metalloproteinases	NK	CD16 shedding	Romee et al., 2013; Coppola et al., 2015
	Tumor	MICA/B, B7-H6, BAG6 shedding	Zhang et al., 2012; Schlecker et al., 2014; Iguchi-Manaka et al., 2016; Rusakiewicz et al., 2017; Zhao Z. et al., 2017; Molfetta et al., 2019