Fig. 4

Determination of MON2 as novel immuno-oncology target. A Presentation of sensitizers and resistors with prognostic significance in TCGA (C2 subtype) and ICB-treated cohorts. The hazard ratio (HR) and corresponding 95% confidence interval (CI) were estimated using a Cox regression model, adjusting for age and cancer type. B Determination of proliferation-independent genes according to the CERES scores from CRISPR knockout screens across hundreds of cancer cell lines. C Intersections between proliferation-independent genes and sensitizer (left) and resistor (right) genes with prognostic significance in both TCGA and ICB-treated cohort. D Coculture assay of MDA-MB-231 cells and antigen-specific T cells. MDA-MB-231 was loaded with Mart1 epitope by lentiviral transduction and cultured in the absence or presence of Mart-1- specific T cells (left panel). MDA-MB-231 cells that express Mart-1-epitope were transduced with Cas9 and then three independent gRNAs targeting MON2. A non-targeting gRNA served as a control. The cells were cultured with or without Mart-1-specific T cells for 24 h (right panel). E Coculture assay of MCF7 cells and antigen-specific T cells. F Association between the functional status of MON2 and clinical response to immunotherapy (CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease) in four ICB-treated datasets. G Pearson correlation between MON2 expression and objective response rate (ORR) for ICB. Only non-zero data was included