PMID- 27994592
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20191120
IS  - 1664-3224 (Print)
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 7
DP  - 2016
TI  - KIR Genes and Their Ligands Predict the Response to Anti-EGFR Monoclonal 
      Antibodies in Solid Tumors.
PG  - 561
LID - 561
AB  - Killer-cell immunoglobulin-like receptors (KIRs) regulate the killing function of 
      natural killer cells, which play an important role in the antibody-dependent 
      cell-mediated cytotoxicity response exerted by therapeutic monoclonal antibodies 
      (mAbs). However, it is unknown whether the extensive genetic variability of KIR 
      genes and/or their human leukocyte antigen (HLA) ligands might influence the 
      response to these treatments. This study aimed to explore whether the variability 
      in KIR/HLA genes may be associated with the variable response observed to mAbs 
      based anti-epidermal growth factor receptor (EGFR) therapies. Thirty-nine 
      patients treated with anti-EGFR mAbs (trastuzumab for advanced breast cancer, or 
      cetuximab for advanced colorectal or advanced head and neck cancer) were included 
      in the study. All the patients had progressed to mAbs therapy and were grouped 
      into two categories taking into account time to treatment failure (TTF </=6 and 
      >/=10 months). KIR genotyping (16 genetic variability) was performed in genomic DNA 
      from peripheral blood by PCR sequence-specific primer technique, and HLA ligand 
      typing was performed for HLA-B and -C loci by reverse polymerase chain reaction 
      sequence-specific oligonucleotide methodology. Subjects carrying the KIR/HLA 
      ligand combinations KIR2DS1/HLAC2C2-C1C2 and KIR3DS1/HLABw4w4-w4w6 showed longer 
      TTF than non-carriers counterparts (14.76 vs. 3.73 months, p < 0.001 and 14.93 
      vs. 4.6 months, p = 0.005, respectively). No other significant differences were 
      observed. Two activating KIR/HLA ligand combinations predict better response of 
      patients to anti-EGFR therapy. These findings increase the overall knowledge on 
      the role of specific gene variants related to responsiveness to anti-EGFR 
      treatment in solid tumors and highlight the importance of assessing gene 
      polymorphisms related to cancer medications.
FAU - Morales-Estevez, Cristina
AU  - Morales-Estevez C
AD  - Medical Oncology Department, IMIBIC, Reina Sofia University Hospital, University 
      of Cordoba , Cordoba , Spain.
FAU - De la Haba-Rodriguez, Juan
AU  - De la Haba-Rodriguez J
AD  - Medical Oncology Department, IMIBIC, Reina Sofia University Hospital, University 
      of Cordoba, Cordoba, Spain; Spanish Cancer Network (RTICC), Instituto de Salud 
      Carlos III, Madrid, Spain.
FAU - Manzanares-Martin, Barbara
AU  - Manzanares-Martin B
AD  - Immunology Department, IMIBIC, Reina Sofia University Hospital, University of 
      Cordoba , Cordoba , Spain.
FAU - Porras-Quintela, Ignacio
AU  - Porras-Quintela I
AD  - Medical Oncology Department, IMIBIC, Reina Sofia University Hospital, University 
      of Cordoba , Cordoba , Spain.
FAU - Rodriguez-Ariza, Antonio
AU  - Rodriguez-Ariza A
AD  - Medical Oncology Department, IMIBIC, Reina Sofia University Hospital, University 
      of Cordoba, Cordoba, Spain; Spanish Cancer Network (RTICC), Instituto de Salud 
      Carlos III, Madrid, Spain.
FAU - Moreno-Vega, Alberto
AU  - Moreno-Vega A
AD  - Medical Oncology Department, IMIBIC, Reina Sofia University Hospital, University 
      of Cordoba , Cordoba , Spain.
FAU - Ortiz-Morales, Maria J
AU  - Ortiz-Morales MJ
AD  - Medical Oncology Department, IMIBIC, Reina Sofia University Hospital, University 
      of Cordoba , Cordoba , Spain.
FAU - Gomez-Espana, Maria A
AU  - Gomez-Espana MA
AD  - Medical Oncology Department, IMIBIC, Reina Sofia University Hospital, University 
      of Cordoba , Cordoba , Spain.
FAU - Cano-Osuna, Maria T
AU  - Cano-Osuna MT
AD  - Medical Oncology Department, IMIBIC, Reina Sofia University Hospital, University 
      of Cordoba , Cordoba , Spain.
FAU - Lopez-Gonzalez, Javier
AU  - Lopez-Gonzalez J
AD  - Medical Oncology Department, IMIBIC, Reina Sofia University Hospital, University 
      of Cordoba , Cordoba , Spain.
FAU - Chia-Delgado, Beatriz
AU  - Chia-Delgado B
AD  - Medical Oncology Department, IMIBIC, Reina Sofia University Hospital, University 
      of Cordoba , Cordoba , Spain.
FAU - Gonzalez-Fernandez, Rafael
AU  - Gonzalez-Fernandez R
AD  - Immunology Department, IMIBIC, Reina Sofia University Hospital, University of 
      Cordoba , Cordoba , Spain.
FAU - Aranda-Aguilar, Enrique
AU  - Aranda-Aguilar E
AD  - Medical Oncology Department, IMIBIC, Reina Sofia University Hospital, University 
      of Cordoba, Cordoba, Spain; Spanish Cancer Network (RTICC), Instituto de Salud 
      Carlos III, Madrid, Spain.
LA  - eng
PT  - Journal Article
DEP - 20161205
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
PMC - PMC5136734
OTO - NOTNLM
OT  - KIR receptor
OT  - KIR/HLA ligands
OT  - advanced cancer
OT  - anti-EGFR
OT  - natural killer cells
OT  - solid tumor
EDAT- 2016/12/21 06:00
MHDA- 2016/12/21 06:01
PMCR- 2016/01/01
CRDT- 2016/12/21 06:00
PHST- 2016/09/29 00:00 [received]
PHST- 2016/11/21 00:00 [accepted]
PHST- 2016/12/21 06:00 [entrez]
PHST- 2016/12/21 06:00 [pubmed]
PHST- 2016/12/21 06:01 [medline]
PHST- 2016/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2016.00561 [doi]
PST - epublish
SO  - Front Immunol. 2016 Dec 5;7:561. doi: 10.3389/fimmu.2016.00561. eCollection 2016.