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Conclusions I HLA-E is generally present and overexpressed in many - - PDF document
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
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Van Esch, CII 2014
Location of CD94/NKG2A expressing T cells (early VIN lesions)
Vulva V N lesions
HLA-E neutralizes the beneficial role of CD8 T cells
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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.
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
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CyTOF phenotyping
Cervical Cx
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Cancer vaccines induce CD8 T cell influx
TC1 mouse tumor
NKG2A is induced on CD8 T cells after cancer vaccination
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CRISPR/Cas9 mediated knockdown of Qa-1b
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Genetic knockdown of mouse HLA-E in tumor cells recapitulates blocking NKG2A mAb data
TC-1 model
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RMA model
Genetic knockdown of mouse HLA-E in lymphoma
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B16 model
Genetic knockdown of mouse HLA-E in melanoma
NK cells are not involved
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RMA model
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10 20 30 40 50 20 40 60 80 100 Days
Survival (%)
Control anti-NKG2A mAb anti-PD-1 mAb anti-NKG2A + anti-PD-1 mAbs * ** ***
NKG2A blockade also improves PD-1 checkpoint therapy
A20 model
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