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Analysis of Human Natural Killer Cell Metabolism
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Interleukin-15 cytokine checkpoints in natural killer cell anti-tumor immunity

Harrison Sudholz1, Rebecca B Delconte2, Nicholas D Huntington3

  • 1Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia.

Current Opinion in Immunology
|July 14, 2023
PubMed

Insights

Immune checkpoint inhibitors (ICIs) show promise but face resistance. Targeting natural killer (NK) cells offers a novel immunotherapy strategy to overcome tumor resistance and improve cancer treatment outcomes.

Area of Science:

  • Immunology
  • Oncology
  • Cancer Immunotherapy

Background:

  • Immune checkpoint inhibitors (ICIs) targeting PD-1, LAG3, and CTLA-4 have transformed cancer treatment.
  • Adaptive resistance, driven by mutations in neoantigen presentation via MHC-I, limits ICI efficacy.
  • Many patients with ICI-responsive tumors like melanoma still do not benefit from monotherapy.

Purpose of the Study:

  • To explore novel immunotherapy strategies beyond T cell checkpoints.
  • To address challenges in treating tumors with low neoantigen/MHC-I expression.
  • To investigate the potential of targeting natural killer (NK) cells to overcome immunotherapy resistance.

Main Methods:

  • Review of current immunotherapy landscape and resistance mechanisms.
  • Analysis of tumor microenvironment factors affecting treatment response.
  • Exploration of NK cell-based therapeutic approaches.

Main Results:

  • Adaptive resistance mechanisms reduce the effectiveness of T cell-based immunotherapies.
  • Tumors with low neoantigen/MHC-I expression present a significant challenge for current treatments.
  • NK cells present a potential alternative or complementary strategy to enhance anti-tumor immunity.

Conclusions:

  • Novel immunotherapies are needed to overcome adaptive resistance and improve patient outcomes.
  • Targeting NK cells may offer a promising avenue to enhance anti-tumor immune responses.
  • NK cell-based strategies could address limitations of current T cell-centric immunotherapies.

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