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2020 Tad Smith & Caroline Fitzgibbons-PCF Young Investigator Award

Defining the Role of Natural Killer Cells in the Radiotherapy Treatment Response of Metastatic Prostate Cancer

Momeneh (Sepideh) Foroutan, PhD

Monash University

Mentors: Shahneen Sandhu, MBBS; Nicholas Huntington, PhD; Joseph Cursons, PhD

Description:

  • 7Lutetium-PSMA (LuPSMA) is a highly promising new type of “radionuclide therapy” treatments that consists of a prostate cancer targeting molecule combined with a radioactive isotope. This treatment thus enables radiation to be delivered systemically, but specifically target and kill prostate cancer cells.
  • Radiation therapy is known to have the potential to activate anti-tumor immune responses, and thus may have synergy with immunotherapies. Clinical trials are underway to evaluate the efficacy of combining LuPSMA with checkpoint immunotherapy in prostate cancer patients. However, the biological impact of these treatment combinations remains to be studied.
  • Dr. Momeneh Foroutan is studying the role of natural killer (NK) immune cells in the efficacy of LuPSMA in patients with metastatic prostate cancer.
  • In this project, Dr. Foroutan will use samples from patients on clinical trials testing LuPSMA combined with checkpoint immunotherapy or PARP-inhibitors to study the biology of NK cells.
  • Whether there are any tumor cell molecular features that correlate with numbers and activity of NK cells in tumors will be investigated.
  • The physical locations, numbers, and activities of NK cells within and surrounding tumors will be investigated in samples from these patients to determine NK cell profiles that correlate with treatment responses.
  • The gene expression profiles of individual NK cells in tumor tissues and in blood will be studied over the course of treatment, to identify NK-based biomarkers that can predict patient outcomes.
  • If successful, this project will reveal the biological role of NK cells and their potential as biomarkers in treatment responses to LuPSMA combined with checkpoint immunotherapy or PARP-inhibitors, and will identify potential targets for NK cell immune therapies.

What this means to patients: Dr. Foroutan is studying NK immune cell biology inpatients treated with LuPSMA combined with checkpoint immunotherapy or PARP-inhibitors. This project may help to identify NK cell biomarkers that are predictive of response to therapy and potential targets that could be used for NK cellimmuno therapy to increase the efficacy of therapy outcome in patients with poor clinical outcome.