PMID- 22788688
OWN - NLM
STAT- MEDLINE
DCOM- 20130401
LR  - 20211021
IS  - 1479-5876 (Electronic)
IS  - 1479-5876 (Linking)
VI  - 10
DP  - 2012 Jul 12
TI  - Biomarkers on melanoma patient T cells associated with ipilimumab treatment.
PG  - 146
LID - 10.1186/1479-5876-10-146 [doi]
AB  - BACKGROUND: Ipilimumab induces long-lasting clinical responses in a minority of 
      patients with metastatic melanoma. To better understand the mechanism(s) of 
      action and to identify novel biomarkers associated with the clinical benefit and 
      toxicity of ipilimumab, baseline characteristics and changes in CD4(+) and CD8(+) 
      T cells from melanoma patients receiving ipilimumab were characterized by gene 
      profiling and flow cytometry. METHODS: Microarray analysis of flow-cytometry 
      purified CD4(+) and CD8(+) T cells was employed to assess gene profiling changes 
      induced by ipilimumab. Selected molecules were further investigated by flow 
      cytometry on pre, 3-month and 6-month post-treatment specimens. RESULTS: 
      Ipilimumab up-regulated Ki67 and ICOS on CD4(+) and CD8(+) cells at both 3- and 
      6-month post ipilimumab (p </= 0.001), decreased CCR7 and CD25 on CD8(+) at 3-month 
      post ipilimumab (p </= 0.02), and increased Gata3 in CD4(+) and CD8(+) cells at 
      6-month post ipilimumab (p </= 0.001). Increased EOMES(+)CD8(+), 
      GranzymeB(+)EOMES(+)CD8(+) and decreased Ki67(+)EOMES(+)CD4(+) T cells at 6 
      months were significantly associated with relapse (all p </= 0.03). Decreased 
      Ki67(+)CD8(+) T cells were significantly associated with the development of irAE 
      (p = 0.02). At baseline, low Ki67(+)EOMES(+)CD8(+) T cells were associated with 
      relapse (p </= 0.001), and low Ki67(+)EOMES(+)CD4(+) T cells were associated with 
      irAE (p </= 0.008). CONCLUSIONS: Up-regulation of proliferation and activation 
      signals in CD4(+) and CD8(+) T cells were pharmacodynamic markers for ipilimumab. 
      Ki67(+)EOMES(+)CD8(+) and Ki67(+)EOMES(+)CD4(+)T cells at baseline merit further 
      testing as biomarkers associated with outcome and irAEs, respectively.
FAU - Wang, Wenshi
AU  - Wang W
AD  - Department of Cutaneous Oncology and the Donald A. Adam Comprehensive Melanoma 
      Research Center, H. Lee Moffitt Cancer Center, Tampa, FL, USA. 
      Wenshi.wang@moffitt.org
FAU - Yu, Daohai
AU  - Yu D
FAU - Sarnaik, Amod A
AU  - Sarnaik AA
FAU - Yu, Bin
AU  - Yu B
FAU - Hall, Maclean
AU  - Hall M
FAU - Morelli, Dawn
AU  - Morelli D
FAU - Zhang, Yonghong
AU  - Zhang Y
FAU - Zhao, Xiuhua
AU  - Zhao X
FAU - Weber, Jeffrey S
AU  - Weber JS
LA  - eng
GR  - P30 CA076292/CA/NCI NIH HHS/United States
GR  - R01 CA 109307/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20120712
PL  - England
TA  - J Transl Med
JT  - Journal of translational medicine
JID - 101190741
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Ipilimumab)
SB  - IM
MH  - Antibodies, Monoclonal/*therapeutic use
MH  - Antineoplastic Agents/*therapeutic use
MH  - Biomarkers, Tumor/*metabolism
MH  - Female
MH  - Flow Cytometry
MH  - Gene Expression Profiling
MH  - Humans
MH  - Ipilimumab
MH  - Male
MH  - Melanoma/*drug therapy/immunology/metabolism/pathology
MH  - Oligonucleotide Array Sequence Analysis
MH  - T-Lymphocytes/*immunology
PMC - PMC3527361
EDAT- 2012/07/14 06:00
MHDA- 2013/04/02 06:00
PMCR- 2012/07/12
CRDT- 2012/07/14 06:00
PHST- 2012/05/22 00:00 [received]
PHST- 2012/05/22 00:00 [accepted]
PHST- 2012/07/14 06:00 [entrez]
PHST- 2012/07/14 06:00 [pubmed]
PHST- 2013/04/02 06:00 [medline]
PHST- 2012/07/12 00:00 [pmc-release]
AID - 1479-5876-10-146 [pii]
AID - 10.1186/1479-5876-10-146 [doi]
PST - epublish
SO  - J Transl Med. 2012 Jul 12;10:146. doi: 10.1186/1479-5876-10-146.