Conclusions I HLA-E is generally present and overexpressed in many - PDF document

05-10-2018 Location of CD94/NKG2A expressing T cells (early VIN lesions) Van Esch, CII 2014 Vulva V N lesions HLA-E neutralizes the beneficial role of CD8 T cells Gooden et al PNAS 2011; van Esch et al CII 2014; van Esch et al Int J Cancer 2014; Talebian Yazdi et al Oncotarget 2015. T van Hall Conclusions I • HLA-E is generally present and overexpressed in many cancers • Positive association with Ag processing molecules • Inhibiting receptor CD94/NKG2A is expressed on tumor infiltrating CD8 T cells • High HLA-E expression neutralizes the survival benefit of CTL infiltration in ovarian cancer 13

05-10-2018 CyTOF phenotyping Cervical Cx T van Hall Cancer vaccines induce CD8 T cell influx TC1 mouse tumor T van Hall NKG2A is induced on CD8 T cells after cancer vaccination TC1 mouse tumor T van Hall 15

05-10-2018 CRISPR/Cas9 mediated knockdown of Qa-1 b T van Hall Genetic knockdown of mouse HLA-E in tumor cells recapitulates blocking NKG2A mAb data TC-1 model T van Hall Genetic knockdown of mouse HLA-E in lymphoma RMA model T van Hall 18

05-10-2018 Genetic knockdown of mouse HLA-E in melanoma B16 model T van Hall NK cells are not involved RMA model T van Hall NKG2A blockade also improves PD-1 checkpoint therapy Control anti-NKG2A mAb anti-PD-1 mAb anti-NKG2A + anti-PD-1 mAbs 100 80 Survival (%) 60 * ** *** 40 20 0 0 10 20 30 40 50 Days A20 model T van Hall 19