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Phenotype and Function of Activated Natural Killer Cells From Patients With Prostate Cancer: Patient-Dependent

Simon P Hood1, Gemma A Foulds1, Heather Imrie2

  • 1John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent University, Nottingham, United Kingdom.

Frontiers in Immunology
|February 15, 2019
PubMed

Insights

Natural killer (NK) cell immunotherapy shows promise for prostate cancer, but effectiveness varies by patient. NK cells can be activated by priming or IL-2, with individual responses dictating the best approach for cancer treatment.

Area of Science:

  • Immunology
  • Oncology
  • Cancer Immunotherapy

Background:

  • Immunotherapy is a promising cancer treatment, but its efficacy in prostate cancer remains limited.
  • Current prostate cancer treatments include radiotherapy and androgen deprivation therapy.
  • Previous research indicated that priming natural killer (NK) cells enhances their cancer-killing ability.

Purpose of the Study:

  • To investigate the phenotype of peripheral blood NK cells in prostate cancer patients.
  • To compare the effectiveness of CTV-1 cell priming versus IL-2 stimulation in activating NK cell cytotoxicity against prostate cancer cells.
  • To explore the patient-specific responses to different NK cell activation methods.

Main Methods:

  • NK cells were isolated from peripheral blood mononuclear cells (PBMCs) of patients with benign conditions and prostate cancer.
  • NK cells were subjected to three conditions: resting, CTV-1 cell priming, or IL-2 activation.
  • Cytotoxicity against PC3 and K562 prostate cancer cell lines was assessed using flow cytometry, with phenotypic analysis and correlation studies.

Main Results:

  • Both NK cell priming and IL-2 activation induced comparable levels of cytotoxicity but resulted in distinct NK cell phenotypes.
  • The response to priming or IL-2 stimulation was patient-dependent and mutually exclusive.
  • Approximately 50% of patients' NK cells responded better to priming, while the other 50% responded better to IL-2 stimulation.

Conclusions:

  • NK cell priming and IL-2 activation offer viable strategies for enhancing NK cell-mediated killing of prostate cancer cells.
  • Patient stratification based on NK cell responsiveness to priming or cytokine stimulation is crucial for personalized immunotherapy.
  • This study supports the development of autologous NK cell-based immunotherapies for prostate cancer treatment.
Keywords:
CTV-1TNF receptorscancercytotoxicitynatural killer (NK) cellsphenotypeprimingprostate

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