¹⁷⁷lu-PSMA-617 radioligand therapy as an immune modulator in prostate cancer

INTRODUCTION: Lu-PSMA-617 has emerged as an effective strategy, and increasing evidence suggests that its activity may extend beyond direct cytotoxicity to the modulation of the tumor immune microenvironment. AREAS COVERED: Lu-PSMA-617 influences immune cell populations, induces immunogenic cell death, and interacts with key microenvironmental factors such as hypoxia, vascularization, and PSMA heterogeneity. The role of alternative radioligands, including alpha-emitters and fibroblast activation protein - targeted agents, is also examined. EXPERT OPINION: PSMA-targeted RLT represents a promising immune-priming modality in mCRPC, but its clinical impact is limited by tumor and microenvironmental heterogeneity. Biomarker-driven patient selection, optimized dosimetry, and rational combination strategies with immunotherapy will be essential to fully exploit its immunomodulatory potential and to achieve durable clinical benefit.