To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3, 9q31.1) and one for endometrioid EOC (5q12.3). We then meta-analysed the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified an additional three loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a novel susceptibility gene for low grade/borderline serous EOC.

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Graphical Abstract Highlights d Anti-4-1BB IgG2a depletes intratumoral Treg cells; IgG1 promotes CD8 T cell function d The efficacy of anti-4-1BB mIgG1 and anti-4-1BB mIgG2a depends on different FcgRs d Optimal tumor therapy requires sequential anti-4-1BB IgG2a and IgG1 or PD-1 blockade d Hinge-engineered anti-4-1BB mIgG2a/h2B mAb harnesses both mechanisms of action

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