RT Journal Article
T1 KIR Genes and Their Ligands Predict the Response to Anti-EGFR Monoclonal Antibodies in Solid Tumors
A1 Morales-Estevez, Cristina
A1 De la Haba-Rodriguez, Juan
A1 Manzanares-Martin, Barbara
A1 Porras-Quintela, Ignacio
A1 Rodriguez-Ariza, Antonio
A1 Moreno-Vega, Alberto
A1 Ortiz-Morales, Maria J.
A1 Gomez-Espana, Maria A.
A1 Cano-Osuna, Maria T.
A1 Lopez-Gonzalez, Javier
A1 Chia-Delgado, Beatriz
A1 Gonzalez-Fernandez, Rafael
A1 Aranda-Aguilar, Enrique
K1 KIR receptor
K1 Anti-EGFR
K1 Advanced cancer
K1 Solid tumor
K1 Natural killer cells
K1 KIR/HLA ligands
K1 Dependent cell cytotoxicity
K1 Hla class-i
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 = 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 IR3DS1/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.
PB Frontiers Research Foundation
SN 1664-3224
YR 2016
FD 2016-11-21
LK http://hdl.handle.net/10668/19220
UL http://hdl.handle.net/10668/19220
LA en
NO Morales-Estevez C, De la Haba-Rodriguez J, Manzanares-Martin B, Porras-Quintela I, Rodriguez-Ariza A, Moreno-Vega A, et al. KIR Genes and Their Ligands Predict the Response to Anti-EGFR Monoclonal Antibodies in Solid Tumors. Front Immunol. 2016 Dec 5;7:561
DS RISalud
RD Apr 8, 2025