PMID- 25232180
OWN - NLM
STAT- MEDLINE
DCOM- 20150526
LR  - 20240210
IS  - 1946-6242 (Electronic)
IS  - 1946-6234 (Linking)
VI  - 6
IP  - 254
DP  - 2014 Sep 17
TI  - Anti-CTLA-4 therapy broadens the melanoma-reactive CD8+ T cell response.
PG  - 254ra128
LID - 10.1126/scitranslmed.3008918 [doi]
AB  - Anti-CTLA-4 treatment improves the survival of patients with advanced-stage 
      melanoma. However, although the anti-CTLA-4 antibody ipilimumab is now an 
      approved treatment for patients with metastatic disease, it remains unknown by 
      which mechanism it boosts tumor-specific T cell activity. In particular, it is 
      unclear whether treatment amplifies previously induced T cell responses or 
      whether it induces new tumor-specific T cell reactivities. Using a combination 
      ultraviolet (UV)-induced peptide exchange and peptide-major histocompatibility 
      complex (pMHC) combinatorial coding, we monitored immune reactivity against a 
      panel of 145 melanoma-associated epitopes in a cohort of patients receiving 
      anti-CTLA-4 treatment. Comparison of pre- and posttreatment T cell reactivities 
      in peripheral blood mononuclear cell samples of 40 melanoma patients demonstrated 
      that anti-CTLA-4 treatment induces a significant increase in the number of 
      detectable melanoma-specific CD8 T cell responses (P = 0.0009). In striking 
      contrast, the magnitude of both virus-specific and melanoma-specific T cell 
      responses that were already detected before start of therapy remained unaltered 
      by treatment (P = 0.74). The observation that anti-CTLA-4 treatment induces a 
      significant number of newly detected T cell responses-but only infrequently 
      boosts preexisting immune responses-provides strong evidence for anti-CTLA-4 
      therapy-enhanced T cell priming as a component of the clinical mode of action.
CI  - Copyright (c) 2014, American Association for the Advancement of Science.
FAU - Kvistborg, Pia
AU  - Kvistborg P
AD  - The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, 
      Netherlands. p.kvistborg@nki.nl t.schumacher@nki.nl.
FAU - Philips, Daisy
AU  - Philips D
AD  - The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, 
      Netherlands.
FAU - Kelderman, Sander
AU  - Kelderman S
AD  - The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, 
      Netherlands.
FAU - Hageman, Lois
AU  - Hageman L
AD  - The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, 
      Netherlands.
FAU - Ottensmeier, Christian
AU  - Ottensmeier C
AD  - National Institute for Health Research Southampton Experimental Cancer Medicine 
      Centre and Southampton University Hospitals, Tremona Road, Southampton, Hampshire 
      SO16 6YD, UK.
FAU - Joseph-Pietras, Deborah
AU  - Joseph-Pietras D
AD  - National Institute for Health Research Southampton Experimental Cancer Medicine 
      Centre and Southampton University Hospitals, Tremona Road, Southampton, Hampshire 
      SO16 6YD, UK.
FAU - Welters, Marij J P
AU  - Welters MJ
AD  - Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, Netherlands.
FAU - van der Burg, Sjoerd
AU  - van der Burg S
AD  - Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, Netherlands.
FAU - Kapiteijn, Ellen
AU  - Kapiteijn E
AD  - Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, Netherlands.
FAU - Michielin, Olivier
AU  - Michielin O
AD  - Ludwig Center for Cancer Research, Department of Oncology, University of 
      Lausanne, Rue Pierre-Decker 4, 1011 Lausanne, Switzerland.
FAU - Romano, Emanuela
AU  - Romano E
AD  - Ludwig Center for Cancer Research, Department of Oncology, University of 
      Lausanne, Rue Pierre-Decker 4, 1011 Lausanne, Switzerland.
FAU - Linnemann, Carsten
AU  - Linnemann C
AD  - The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, 
      Netherlands.
FAU - Speiser, Daniel
AU  - Speiser D
AD  - Ludwig Center for Cancer Research, Department of Oncology, University of 
      Lausanne, Rue Pierre-Decker 4, 1011 Lausanne, Switzerland.
FAU - Blank, Christian
AU  - Blank C
AD  - The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, 
      Netherlands.
FAU - Haanen, John B
AU  - Haanen JB
AD  - The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, 
      Netherlands.
FAU - Schumacher, Ton N
AU  - Schumacher TN
AD  - The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, 
      Netherlands. p.kvistborg@nki.nl t.schumacher@nki.nl.
LA  - eng
GR  - 15951/CRUK_/Cancer Research UK/United Kingdom
PT  - Journal Article
PL  - United States
TA  - Sci Transl Med
JT  - Science translational medicine
JID - 101505086
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (CTLA-4 Antigen)
RN  - 0 (Ipilimumab)
SB  - IM
MH  - Antibodies, Monoclonal/immunology/*therapeutic use
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - CTLA-4 Antigen/*immunology
MH  - Humans
MH  - *Immunotherapy
MH  - Ipilimumab
MH  - Melanoma/immunology/*therapy
EDAT- 2014/09/19 06:00
MHDA- 2015/05/27 06:00
CRDT- 2014/09/19 06:00
PHST- 2014/09/19 06:00 [entrez]
PHST- 2014/09/19 06:00 [pubmed]
PHST- 2015/05/27 06:00 [medline]
AID - 6/254/254ra128 [pii]
AID - 10.1126/scitranslmed.3008918 [doi]
PST - ppublish
SO  - Sci Transl Med. 2014 Sep 17;6(254):254ra128. doi: 10.1126/scitranslmed.3008918.