PMID- 19223507
OWN - NLM
STAT- MEDLINE
DCOM- 20090414
LR  - 20091119
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 15
IP  - 5
DP  - 2009 Mar 1
TI  - CD8 T-cell responses against cyclin B1 in breast cancer patients with tumors 
      overexpressing p53.
PG  - 1543-9
LID - 10.1158/1078-0432.CCR-08-1412 [doi]
AB  - PURPOSE: This study aimed to examine CD8 T-cell reactivity in breast cancer 
      patients against cyclin B1-derived peptides restricted by the human leukocyte 
      antigen (HLA)-A2 molecule. EXPERIMENTAL DESIGN: Peripheral blood mononuclear 
      cells from 36 breast cancer patients were analyzed by enzyme-linked immunosorbent 
      spot (ELISPOT) for the presence of T cells recognizing the cyclin B1-derived 
      peptides CB9 (AKYLMELTM) and CB-P4 (AKYLMELCC), in addition to modified versions 
      of CB9, CB9L2 (ALYLMELTM) and CB9M2 (AMYLMELTM), both of which display higher 
      affinity to HLA-A2. RESULTS: Twelve patients harbored a memory CD8 T-cell 
      response against at least one of the peptides; strongest reactivity was detected 
      against the CB9L2 peptide. Because the level of cyclin B1 has been shown to be 
      influenced by the level of p53, which in turn is elevated in cancer cells because 
      of point mutation, we analyzed the level of p53 protein in biopsies from the 
      patients by immune histochemistry. Combined data showed that anti-cyclin B1 
      reactivity was predominantly detected in patients with tumors characterized by 
      elevated expression of p53. Interestingly, no reactivity was detected against six 
      peptides derived from the p53 protein. CONCLUSIONS: Our data support the notion 
      of cyclin B1 as a prominent target for immunologic recognition in cancer patients 
      harboring p53-mutated cancer cells. Because mutation of p53 is one of the most 
      frequent genetic alterations in human cancers, this suggests that immunotherapy 
      based on targeting of cyclin B1 is broadly applicable in a large proportion of 
      cancer patients.
FAU - Sorensen, Rikke Baek
AU  - Sorensen RB
AD  - Center for Cancer Immune Therapy, Department of Hematology, University Hospital 
      Herlev, Herlev Ringvej, Denmark.
FAU - Andersen, Rikke Sick
AU  - Andersen RS
FAU - Svane, Inge Marie
AU  - Svane IM
FAU - Engell-Noerregaard, Lotte
AU  - Engell-Noerregaard L
FAU - Hadrup, Sine R
AU  - Hadrup SR
FAU - Balslev, Eva
AU  - Balslev E
FAU - Andersen, Mads Hald
AU  - Andersen MH
FAU - thor Straten, Per
AU  - thor Straten P
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090217
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (CCNB1 protein, human)
RN  - 0 (Cyclin B)
RN  - 0 (Cyclin B1)
RN  - 0 (HLA-A2 Antigen)
RN  - 0 (Peptide Fragments)
RN  - 0 (TP53 protein, human)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
CIN - Clin Cancer Res. 2009 Nov 15;15(22):7106; author reply 7106-7. PMID: 19903794
MH  - Adult
MH  - Aged
MH  - Breast Neoplasms/*immunology/pathology
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Case-Control Studies
MH  - Cyclin B/*immunology
MH  - Cyclin B1
MH  - Female
MH  - Flow Cytometry
MH  - HLA-A2 Antigen/metabolism
MH  - Humans
MH  - Immunoenzyme Techniques
MH  - Interferon-gamma/metabolism
MH  - Middle Aged
MH  - Mutation
MH  - Peptide Fragments/*immunology
MH  - Tumor Suppressor Protein p53/*metabolism
EDAT- 2009/02/19 09:00
MHDA- 2009/04/15 09:00
CRDT- 2009/02/19 09:00
PHST- 2009/02/19 09:00 [entrez]
PHST- 2009/02/19 09:00 [pubmed]
PHST- 2009/04/15 09:00 [medline]
AID - 1078-0432.CCR-08-1412 [pii]
AID - 10.1158/1078-0432.CCR-08-1412 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2009 Mar 1;15(5):1543-9. doi: 10.1158/1078-0432.CCR-08-1412. 
      Epub 2009 Feb 17.