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KIR Genes and Their Ligands Predict the Response to Anti-EGFR Monoclonal Antibodies in Solid Tumors

Overview of attention for article published in Frontiers in immunology, December 2016
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Title
KIR Genes and Their Ligands Predict the Response to Anti-EGFR Monoclonal Antibodies in Solid Tumors
Published in
Frontiers in immunology, December 2016
DOI 10.3389/fimmu.2016.00561
Pubmed ID
Authors

Cristina Morales-Estevez, Juan De la Haba-Rodriguez, Barbara Manzanares-Martin, Ignacio Porras-Quintela, Antonio Rodriguez-Ariza, Alberto Moreno-Vega, Maria J. Ortiz-Morales, Maria A. Gomez-España, Maria T. Cano-Osuna, Javier Lopez-Gonzalez, Beatriz Chia-Delgado, Rafael Gonzalez-Fernandez, Enrique Aranda-Aguilar

Abstract

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.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 31 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Spain 1 3%
Unknown 30 97%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 6 19%
Researcher 4 13%
Student > Master 4 13%
Student > Doctoral Student 3 10%
Unspecified 1 3%
Other 0 0%
Unknown 13 42%
Readers by discipline Count As %
Medicine and Dentistry 8 26%
Biochemistry, Genetics and Molecular Biology 4 13%
Immunology and Microbiology 4 13%
Mathematics 1 3%
Unspecified 1 3%
Other 1 3%
Unknown 12 39%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 07 December 2016.
All research outputs
#14,783,688
of 25,373,627 outputs
Outputs from Frontiers in immunology
#12,923
of 31,516 outputs
Outputs of similar age
#214,045
of 416,422 outputs
Outputs of similar age from Frontiers in immunology
#133
of 261 outputs
Altmetric has tracked 25,373,627 research outputs across all sources so far. This one is in the 41st percentile – i.e., 41% of other outputs scored the same or lower than it.
So far Altmetric has tracked 31,516 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.4. This one has gotten more attention than average, scoring higher than 58% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 416,422 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 48th percentile – i.e., 48% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 261 others from the same source and published within six weeks on either side of this one. This one is in the 48th percentile – i.e., 48% of its contemporaries scored the same or lower than it.