RT Book, Section
A1 Quezada, Sergio A.
A1 Peggs, Karl S.
A2 Kaushansky, Kenneth
A2 Prchal, Josef T.
A2 Burns, Linda J.
A2 Lichtman, Marshall A.
A2 Levi, Marcel
A2 Linch, David C.
SR Print(0)
ID 1178737701
T1 Immune Checkpoint Inhibitors
T2 Williams Hematology, 10e
YR 2021
FD 2021
PB McGraw-Hill Education
PP New York, NY
SN 9781260464122
LK hemonc.mhmedical.com/content.aspx?aid=1178737701
RD 2024/04/18
AB SUMMARYT-cell  function  is  tightly  regulated  in  order  to  prevent  inappropriate  activation  or  collateral  damage  during  productive  immune  responses.  One  of  the  critical  cell  intrinsic  regulatory  elements  is  a  series  of  inhibitory  cell  surface  receptors.  In  normal  immune  responses,  the  integration  of  signaling  from  the  T-cell  receptor  (signal  1),  costimulatory  and  coinhibitory  receptors  (signal  2),  and  further  signals  provided  by  cytokines  (signal  3)  determine  cell  fate  and  activation  status.  Lack  of  appropriate  stimulatory  elements  or  an  abundance  of  inhibitory  signals  can  drive  anergy  or  exhaustion,  preventing  the  immune  system  from  responding  to  foreign  antigens,  particularly  those  presented  chronically  such  as  cancer  neoantigens.  Multiple  elements  of  this  rheostatic  system  are  therefore  potentially  targetable  to  enhance  immunity  for  therapeutic  benefit.  Drugs  targeting  the  inhibitory  signaling  pathway  checkpoints  (checkpoint  inhibitors)  have  shown  efficacy  in  several  human  cancers,  including  hematologic  malignancies,  forming  the  basis  for  the  award  of  the  Nobel  Prize  for  Medicine  in  2018  to  James  P.  Allison  and  Tasuku  Honjo  “for  their  discovery  of  cancer  therapy  by  inhibition  of  negative  immune  regulation.”  Insights  into  the  pathways  most  relevant  for  immune  evasion  in  specific  cancers  have  underpinned  significant  clinical  progress  and  offer  promising  areas  for  future  research,  often  in  combination  with  other  therapeutic  modalities.