AUTHOR=Li Xiaoya , Yang Fang , Wang Meijing , Huang Xiaopeng , Zeng Xin , Zhou Lu , Peng Sixue , Zhang Jingyi 

TITLE=Unleashing the power of peptides in prostate cancer immunotherapy: mechanism, facts and perspectives

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1478331

DOI=10.3389/fphar.2025.1478331

ISSN=1663-9812

ABSTRACT=Prostate cancer, the second most common cancer in men, often progresses to castration-resistant prostate cancer despite androgen deprivation therapy. Immunotherapy, revolutionary in cancer treatment, has limited efficacy in prostate cancer due to its “cold tumor” nature. Peptides, with unique advantages, offer new hope. This review explores how peptide-based tumor immunotherapy can transform prostate cancer from a “cold” to a “hot” state. It modulates the immunosuppressive tumor microenvironment by regulating non-immune cells (such as cancer-associated fibroblasts, endothelial cells, and adipose stromal cells), repolarizing tumor-associated macrophages, activating NK cells, and tuning cytokines. Additionally, peptides can induce immunogenic cell death (ICD) in prostate cancer cells through ferroptosis, pyroptosis, and autophagy modulation. The review also revisits existing prostate cancer immunotherapies, including immune checkpoint blockade, CAR T cell therapy, and dendritic cell vaccines, highlighting how peptides can enhance their effectiveness and safety. Finally, two peptide-based immunotherapy strategies in the development stage, peptide-integrated Proteolysis-Targeting Chimera therapy and peptide-involved epigenomic therapy, are introduced, showing great potential for future prostate cancer treatment.