KIR-HLA Functional Repertoire Influences Trastuzumab Efficiency in Patients With HER2-Positive Breast Cancer.
Adult
Aged
Antibodies, Monoclonal, Humanized
/ therapeutic use
Antibody-Dependent Cell Cytotoxicity
/ drug effects
Breast Neoplasms
/ drug therapy
Female
HLA Antigens
/ metabolism
Histocompatibility Antigens Class I
/ metabolism
Humans
Killer Cells, Natural
/ drug effects
Middle Aged
Neoadjuvant Therapy
/ methods
Prognosis
Receptor, ErbB-2
/ metabolism
Receptors, KIR
/ metabolism
Trastuzumab
/ therapeutic use
Young Adult
ADCC
HLA
KIR
breast cancer
trastuzumab
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2021
2021
Historique:
received:
09
10
2021
accepted:
20
12
2021
entrez:
31
1
2022
pubmed:
1
2
2022
medline:
22
2
2022
Statut:
epublish
Résumé
Trastuzumab induced a high rate of pathological Complete Response (pCR) in patients affected by locally advanced HER2-positive Breast Cancer (HER2-BC), by exploiting immune-mediated mechanisms as Antibody-Dependent Cell Cytotoxicity (ADCC) involving Natural Killer (NK) cells. Host's immune genetics could influence the response to therapy, through the expression of variants that characterize NK receptors involved in ADCC effectiveness. Killer cell immunoglobin-like receptors (KIRs) modulate NK cell activity through their binding to class-I Human Leukocyte Antigens (HLA). The impact of the KIR/HLA repertoire in HER2-BC is under study. We characterized KIR genotypes of 36 patients with locally advanced HER2-BC treated with neoadjuvant chemotherapy including trastuzumab. We monitored pCR achievement before surgery and Disease-Free Survival (DFS) and Overall Survival (OS) after adjuvant therapy. HLA, and Fc gamma receptor IIIa (FcγR3A) and IIa (FcγR2A) were genotyped through targeted PCR and Sanger sequencing in 35/36 patients. The KIR-HLA combinations were then described as functional haplotypes and divided in two main categories as inhibitory tel A and stimulatory tel B. Trastuzumab-dependent ADCC activity was monitored with an
Identifiants
pubmed: 35095867
doi: 10.3389/fimmu.2021.791958
pmc: PMC8790064
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
HLA Antigens
0
Histocompatibility Antigens Class I
0
Receptors, KIR
0
ERBB2 protein, human
EC 2.7.10.1
Receptor, ErbB-2
EC 2.7.10.1
Trastuzumab
P188ANX8CK
Banques de données
ClinicalTrials.gov
['NCT02307227']
Types de publication
Clinical Trial, Phase II
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
791958Informations de copyright
Copyright © 2022 Muraro, De Zorzi, Miolo, Lombardi, Scalone, Spazzapan, Massarut, Perin, Dolcetti, Steffan and De Re.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The editor PL declared a past co-authorship with one of the authors VR at the time of review.
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