patient-derived tumor cell lines; I.K.Z. and J.M.R. generated and provided cells from an ovarian cancer PDX model; P.B. provided CLL samples for analysis. W.Z. provided expert technical assistance. T.E. generated RNA-seq data for mono-allelic cell lines; T.O. and T.L. generated and quantified Ribo-seq data.

2 11 newly generated MCC lines through genomic and proteomic analysis. We then interrogated MCC lines through genome-scale gain-and loss-of-function screens for the restoration of HLA-I. These screens identified MYCL and the non-canonical Polycomb repressive complex 1.1 (PRC1.1) as regulators of HLA-I. We further demonstrate that pharmacologic inhibition of the PRC1.1 component USP7 can restore HLA-I expression.

No abstract