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Emerging roles of KIR2DL4 in cancer immunotherapy

Weimiao Li1, Guoxu Zheng2, Shuqun Zhang3

  • 1The Comprehensive Breast Care Center, The Second Affiliated Hospital of Xi'an Jiaotong University, No.157, Xiwu Road, Xi'an, 710004, China.

Breast Cancer (Tokyo, Japan)
|June 23, 2025
PubMed

Insights

Killer-cell immunoglobulin-like receptor 2DL4 (KIR2DL4) is a key immune checkpoint on natural killer (NK) cells. Targeting KIR2DL4 shows promise for enhancing antitumor immune responses and developing novel cancer immunotherapies.

Area of Science:

  • Immunology
  • Cancer Biology
  • Molecular Medicine

Background:

  • Killer-cell immunoglobulin-like receptor 2DL4 (KIR2DL4) is expressed on natural killer (NK) cells and interacts with Human Leucocyte Antigen-G (HLA-G).
  • KIR2DL4 plays a role in immune regulation and has been implicated in tumor evasion in various cancers.
  • Elevated KIR2DL4 expression is observed in melanoma, lung, and ovarian cancers.

Purpose of the Study:

  • To review and discuss the potential of KIR2DL4 as a target for cancer immunotherapy.
  • To highlight the role of KIR2DL4 in tumor immune evasion and its potential as an immune checkpoint.
  • To explore the development of novel KIR2DL4-targeted therapies.

Main Methods:

  • Literature review of studies investigating KIR2DL4 function in cancer.
  • Analysis of KIR2DL4 expression patterns in different tumor types.
  • Discussion of previous findings on KIR2DL4 blockade in preclinical models.

Main Results:

  • KIR2DL4 blockade can re-sensitize breast cancer to trastuzumab treatment, identifying KIR2DL4 as a pivotal NK cell immune checkpoint.
  • KIR2DL4 is expressed in several cancer types, suggesting its involvement in tumor immune evasion.
  • Current therapeutic strategies targeting KIRs exist, but none are specifically efficient for KIR2DL4.

Conclusions:

  • KIR2DL4 is a promising target for enhancing antitumor immunity.
  • Further understanding of KIR2DL4's role may lead to effective KIR2DL4-targeted cancer immunotherapies.
  • Developing KIR2DL4-targeted therapies could offer new treatment options for cancer patients.

Keywords:
Cancer immunotherapyImmune checkpointKIR2DL4NK cells

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