PMID- 33846431
OWN - NLM
STAT- MEDLINE
DCOM- 20211104
LR  - 20230130
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 11
IP  - 1
DP  - 2021 Apr 12
TI  - Coexistence of inhibitory and activating killer-cell immunoglobulin-like 
      receptors to the same cognate HLA-C2 and Bw4 ligands confer breast cancer risk.
PG  - 7932
LID - 10.1038/s41598-021-86964-y [doi]
LID - 7932
AB  - Human leukocyte antigen (HLA) class I-specific killer-cell immunoglobulin-like 
      receptors (KIR) regulate natural killer (NK) cell function in eliminating 
      malignancy. Breast cancer (BC) patients exhibit reduced NK-cytotoxicity in 
      peripheral blood. To test the hypothesis that certain KIR-HLA combinations 
      impairing NK-cytotoxicity predispose to BC risk, we analyzed KIR and HLA 
      polymorphisms in 162 women with BC and 278 controls. KIR-Bx genotypes increased 
      significantly in BC than controls (83.3% vs. 71.9%, OR 1.95), and the increase 
      was more pronounced in advanced-cancer (OR 5.3). No difference was observed with 
      inhibitory KIR (iKIR) and HLA-ligand combinations. The activating KIR (aKIR) and 
      HLA-ligand combinations, 2DS1 + C2 (OR 2.98) and 3DS1 + Bw4 (OR 2.6), were 
      significantly increased in advanced-BC. All patients with advanced-cancer 
      carrying 2DS1 + C2 or 3DS1 + Bw4 also have their iKIR counterparts 2DL1 and 3DL1, 
      respectively. Contrarily, the 2DL1 + C2 and 3DL1 + Bw4 pairs without their aKIR 
      counterparts are significantly higher in controls. These data suggest that NK 
      cells expressing iKIR to the cognate HLA-ligands in the absence of putative aKIR 
      counterpart are instrumental in antitumor response. These data provide a new 
      framework for improving the utility of genetic risk scores for individualized 
      surveillance.
FAU - Ashouri, Elham
AU  - Ashouri E
AD  - UCLA Immunogenetics Center, David Geffen School of Medicine at UCLA, University 
      of California, Los Angeles, CA, 90095, USA.
AD  - Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of 
      Medical Sciences, Shiraz, Iran.
FAU - Rajalingam, Karan
AU  - Rajalingam K
AD  - UCLA Immunogenetics Center, David Geffen School of Medicine at UCLA, University 
      of California, Los Angeles, CA, 90095, USA.
FAU - Barani, Shaghik
AU  - Barani S
AD  - Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of 
      Medical Sciences, Shiraz, Iran.
FAU - Farjadian, Shirin
AU  - Farjadian S
AD  - Department of Immunology, School of Medicine, Shiraz University of Medical 
      Sciences, Shiraz, Iran.
FAU - Ghaderi, Abbas
AU  - Ghaderi A
AD  - Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of 
      Medical Sciences, Shiraz, Iran.
FAU - Rajalingam, Raja
AU  - Rajalingam R
AD  - UCLA Immunogenetics Center, David Geffen School of Medicine at UCLA, University 
      of California, Los Angeles, CA, 90095, USA. Rajalingam.Raja@ucsf.edu.
AD  - Immunogenetics and Transplantation Laboratory, Department of Surgery, University 
      of California San Francisco, San Francisco, CA, USA. Rajalingam.Raja@ucsf.edu.
LA  - eng
PT  - Journal Article
DEP - 20210412
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (HLA-B Antigens)
RN  - 0 (HLA-Bw4 antigen)
RN  - 0 (HLA-C Antigens)
RN  - 0 (Ligands)
RN  - 0 (Receptors, KIR)
SB  - IM
MH  - Breast Neoplasms/genetics/*immunology/pathology
MH  - Case-Control Studies
MH  - Female
MH  - HLA-B Antigens/*metabolism
MH  - HLA-C Antigens/*metabolism
MH  - Haplotypes/genetics
MH  - Heterozygote
MH  - Humans
MH  - Ligands
MH  - Neoplasm Staging
MH  - Receptors, KIR/*metabolism
MH  - Risk Factors
PMC - PMC8041876
COIS- The authors declare no competing interests.
EDAT- 2021/04/14 06:00
MHDA- 2021/11/05 06:00
PMCR- 2021/04/12
CRDT- 2021/04/13 06:08
PHST- 2021/01/05 00:00 [received]
PHST- 2021/03/17 00:00 [accepted]
PHST- 2021/04/13 06:08 [entrez]
PHST- 2021/04/14 06:00 [pubmed]
PHST- 2021/11/05 06:00 [medline]
PHST- 2021/04/12 00:00 [pmc-release]
AID - 10.1038/s41598-021-86964-y [pii]
AID - 86964 [pii]
AID - 10.1038/s41598-021-86964-y [doi]
PST - epublish
SO  - Sci Rep. 2021 Apr 12;11(1):7932. doi: 10.1038/s41598-021-86964-y.