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Platinum Priority – Editorial Referring to the article published on pp. x–y of this issue|Articles in Press

Development of Novel Regimens Combining Immune Checkpoint Inhibitors and Radiation Therapy in Prostate Cancer

Published:December 08, 2021DOI:https://doi.org/10.1016/j.eururo.2021.11.024
      Immune checkpoint inhibitors (ICIs) directed against CTLA-4 or PD-1 or its ligand PD-L1 have been approved for multiple tumor types after improvement in survival outcomes with these agents was demonstrated. However, in prostate cancer, ICI registration trials such as CA184-095 and IMbassador 250 that explored these agents either alone or in combination with an androgen axis inhibitor have not yet yielded clinical success [
      • Venkatachalam S.
      • McFarland T.R.
      • Agarwal N.
      • Swami U.
      Immune checkpoint inhibitors in prostate cancer.
      ]. This is largely because of the immunologically “cold” nature of prostate cancer, which is probably driven by multiple factors such as low tumor mutational burden, predominance of immunosuppressive cells in the tumor microenvironment, lower expression of the major histocompatibility complex class I molecule, and dysfunctional interferon-1 signaling [
      • Venkatachalam S.
      • McFarland T.R.
      • Agarwal N.
      • Swami U.
      Immune checkpoint inhibitors in prostate cancer.
      ]. To overcome these hurdles, multiple studies are currently investigating the rationale for combining ICIs with poly(ADP-ribose) polymerase (PARP) inhibitors, radiation therapy, radiopharmaceuticals, and other immunomodulatory agents such as tumor vaccines, chemotherapy, and tyrosine kinase inhibitors [
      • Venkatachalam S.
      • McFarland T.R.
      • Agarwal N.
      • Swami U.
      Immune checkpoint inhibitors in prostate cancer.
      ].
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        Immune checkpoint inhibitors in prostate cancer.
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