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Immunotherapyoflymphomas
Thewayforward?
Y.L.Kwong
UniversityDepartmentofMedicine
QueenMaryHospital
TwosignalmodelofT-cellactivation
1.T-cellactivation
2.Subsetdifferentiation
3.Effectorfunction
4.Motility
5.Survival
InteractionswithAPC:stimulatory
Chen&Flies,NatRevImmunol2013
InteractionswithAPC:inhibitory
Chen&Flies,NatRevImmunol2013
InteractionswithAPC
Chen&Flies,NatRevImmunol2013
InteractionswithAPC:T-cellinhibitorysignals
Nguyen&Ohashi,NatRevImmunol2015
Targetable
Molecules
CTLA4
PD1
LAG3
TIM3
InteractionswithAPC:T-cellinhibitorysignals
Nguyen&Ohashi,NatRevImmunol2015
TargetablemoleculesoneffectorT-cells
Batlevietal,NatRevClinOncol2016
TargetablemoleculesoneffectorT-cells
Batlevietal,NatRevClinOncol2016
T-cellengagementinlymphnode
Batlevietal,NatRevClinOncol2016
T-cellengagementinthetumour
Batlevietal,NatRevClinOncol2016
MechanismsofPDL1expression
Topalianetal,CancerCell2015
Anti-tumourimmunity
Sharma&Allison,Cell2015
Anti-tumorimmunity:aprimer
Sharma&Allison,Cell2015
Immunecheckpointtherapy
TargetingPD1
•Hodgkinlymphoma
•NK/T-celllymphoma
•Anaplasticlargecelllymphoma
•Doublehitlymphoma
Immunecheckpointtherapy
In
ClassicalHodgkinlymphoma
CASE1
Casepresentation:refractoryHL
•20-year-oldmanfromPortugal
•NodularsclerosingHodgkinlymphoma
•6coursesofABVD-residualdisease
•3morecoursesofABVD-stillPET/CTpositive
•Referredforfurthertreatment
Casepresentation:refractoryHL
ResidualdiseaseaftersalvagewithDHAPx2
Mediastinallymphnodes
Casepresentation:refractoryHL
ResidualdiseaseaftersalvagewithDHAPx2
Thoracicvertebralbody
Casepresentation:refractoryHL
•Secondsalvagewithonecourseofetoposide,cisplatin,ifosfamideandgemcitabine
•Stillpalpablecervicallymphnodes
•Thirdsalvagewith2coursesofbendamustine
Cas
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