PMID- 35185887
OWN - NLM
STAT- MEDLINE
DCOM- 20220330
LR  - 20220330
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 13
DP  - 2022
TI  - Roles of HLA-G/KIR2DL4 in Breast Cancer Immune Microenvironment.
PG  - 791975
LID - 10.3389/fimmu.2022.791975 [doi]
LID - 791975
AB  - Human leukocyte antigen (HLA)-G is a nonclassical MHC Class I molecule, which was 
      initially reported as a mediator of immune tolerance when expressed in 
      extravillous trophoblast cells at the maternal-fetal interface. HLA-G is the only 
      known ligand of killer cell immunoglobulin-like receptor 2DL4 (KIR2DL4), an 
      atypical family molecule that is widely expressed on the surface of NK cells. 
      Unlike other KIR receptors, KIR2DL4 contains both an arginine-tyrosine activation 
      motif in its transmembrane region and an immunoreceptor tyrosine-based inhibitory 
      motif (ITIM) in its cytoplasmic tail, suggesting that KIR2DL4 may function as an 
      activating or inhibitory receptor. The immunosuppressive microenvironment 
      exemplified by a rewired cytokine network and upregulated immune checkpoint 
      proteins is a hallmark of advanced and therapy-refractory tumors. Accumulating 
      evidence has shown that HLA-G is an immune checkpoint molecule with specific 
      relevance in cancer immune escape, although the role of HLA-G/KIR2DL4 in 
      antitumor immunity is still uncharacterized. Our previous study had shown that 
      HLA-G was a pivotal mediator of breast cancer resistance to trastuzumab, and 
      blockade of the HLA-G/KIR2DL4 interaction can resensitize breast cancer to 
      trastuzumab treatment. In this review, we aim to summarize and discuss the role 
      of HLA-G/KIR2DL4 in the immune microenvironment of breast cancer. A better 
      understanding of HLA-G is beneficial to identifying novel biomarker(s) for breast 
      cancer, which is important for precision diagnosis and prognostic assessment. In 
      addition, it is also necessary to unravel the mechanisms underlying HLA-G/KIR2DL4 
      regulation of the immune microenvironment in breast cancer, hopefully providing a 
      rationale for combined HLA-G and immune checkpoints targeting for the effective 
      treatment of breast cancer.
CI  - Copyright (c) 2022 Zheng, Jia and Yang.
FAU - Zheng, Guoxu
AU  - Zheng G
AD  - State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military 
      Medical University, Xi'an, China.
FAU - Jia, Lintao
AU  - Jia L
AD  - State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular 
      Biology, Fourth Military Medical University, Xi'an, China.
FAU - Yang, An-Gang
AU  - Yang AG
AD  - State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military 
      Medical University, Xi'an, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20220203
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (HLA-G Antigens)
RN  - 0 (KIR2DL4 protein, human)
RN  - 0 (Receptors, KIR2DL4)
SB  - IM
MH  - Breast Neoplasms/*genetics/immunology/pathology
MH  - Drug Resistance, Neoplasm/genetics/immunology
MH  - Female
MH  - HLA-G Antigens/*genetics/immunology
MH  - Humans
MH  - Killer Cells, Natural/immunology
MH  - Receptors, KIR2DL4/*genetics/immunology
MH  - Tumor Microenvironment/*genetics/immunology
PMC - PMC8850630
OTO - NOTNLM
OT  - HLA-G
OT  - KIR2DL4
OT  - breast cancer
OT  - immune microenvironment
OT  - immunotherapy
COIS- 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.
EDAT- 2022/02/22 06:00
MHDA- 2022/03/31 06:00
PMCR- 2022/01/01
CRDT- 2022/02/21 06:01
PHST- 2021/10/09 00:00 [received]
PHST- 2022/01/19 00:00 [accepted]
PHST- 2022/02/21 06:01 [entrez]
PHST- 2022/02/22 06:00 [pubmed]
PHST- 2022/03/31 06:00 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2022.791975 [doi]
PST - epublish
SO  - Front Immunol. 2022 Feb 3;13:791975. doi: 10.3389/fimmu.2022.791975. eCollection 
      2022.