Nucleolar TAAP1/C22orf46 confers pro-survival signaling in non-small cell lung cancer

Tumor cells subvert immune surveillance by harnessing inhibitory signals to acquire immune resistance. Bispecific antibodies have been developed to direct cytotoxic T lymphocytes to the tumor site and foster their activities to reduce tumor immune resistance. Although applied with success, bispecific antibodies are not universally effective partially due to the expression of pro-survival factors by tumor cells. Here, we report a CRISPR/Cas9 screen in human non-small cell lung cancer for genes that confer tumors with increased resistance to T lymphocyte mediated killing. We show that lung carcinoma cells devoid of expression of the gene C22orf46 exhibit increased susceptibility to T cell induced apoptosis and genotoxic stress mediated by chemotherapeutic agents. We present data showing that C22orf46, previously annotated as a non-coding gene, encodes an expressed nucleolar protein with remote homologies to the BH domain-containing Bcl-2 family and propose to name this protein Tumor Apoptosis Associated Protein 1 (TAAP1). Collectively, our findings establish TAAP1/C22orf46 as a pro-survival oncogene with possible implications to therapy Overall design: RNA-seq transcriptome profiling of wild-type and C22orf46-knockout NCI-H1975 cells, with both genotypes cultured and sequenced in triplicates.