Human Cancers Express TRAILshort, a Dominant Negative TRAIL Splice Variant, Which Impairs Immune Effector Cell Killing of Tumor Cells.

ABSTRACT:

Purpose

TNF-related apoptosis inducing ligand (TRAIL) expression by immune cells contributes to antitumor immunity. A naturally occurring splice variant of TRAIL, called TRAILshort, antagonizes TRAIL-dependent cell killing. It is unknown whether tumor cells express TRAILshort and if it impacts antitumor immunity.

Experimental design

We used an unbiased informatics approach to identify TRAILshort expression in primary human cancers, and validated those results with IHC and ISH. TRAILshort-specific mAbs were used to determine the effect of TRAILshort on tumor cell sensitivity to TRAIL, and to immune effector cell dependent killing of autologous primary tumors.

Results

As many as 40% of primary human tumors express TRAILshort by both RNA sequencing and IHC analysis. By I

SUBMITTER: Aboulnasr F 

PROVIDER: S-EPMC7642027 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature