Apoptosis of tumor-infiltrating T lymphocytes: a new immune checkpoint mechanism

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Published online 2018 Nov 7. doi: 10.1007/s00262-018-2269-y

Table 1

Potential benefits of inhibiting the Fas–FasL pathway in cancer therapy

Consequences of Fas neutralization	Mode of Fas inhibition	Evidence	References
Immune-mediated effects
Inhibiting the immune checkpoint relying on AICD	Fas antagonist antibody and FasFc	In vitro	[23]
	Fas and FasL silencing	In vitro	[114]
	Drug-induced FasL suppression	In vitro and in vivo	[115]
Preventing TIL apoptosis induced by MDSC	FasFc and Fas silencing in CD8 T cells	In vitro and in vivo	[7]
Preventing TIL apoptosis induced by MDSC	FasL KO mice	In vivo	[64]
Preventing apoptosis induced by endothelial cells	Anti-FasL antibody and gld mice (FasL KO)	In vivo	[54]
Protecting CD8 T cells from tumor cell-mediated Fas counterattack	Anti-FasL antibody	In vitro	[116]
Preventing precocious differentiation of naive T cells	Anti-FasL antibody	In vitro and in vivo	[33]
Preventing APC apoptosis	APC KO for Fas	In vitro and in vivo	[79]
Non immune-mediated effects
Inhibiting glioma invasiveness	Fas–Fc	In vitro	[44]
	Fas–Fc	In vivo (human)	[49]
	Anti-FasL neutralizing antibody	In vitro and in vivo	[45]
	Recombinant Fas extracellular domain	In vitro	[47]
Preventing metastatic spread of pancreatic ductal carcinoma	Fas–Fc	In vivo	[50]