Related Experiment Video
Updated: May 7, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
177Lu-PSMA-617 radioligand therapy as an immune modulator in prostate cancer
Carolina Sciortino1, Amedeo Nuzzo1, Marco Stellato1
1Genitourinary Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy.
Introduction:
Metastatic castration-resistant prostate cancer (mCRPC) remains a therapeutic challenge despite advances in systemic treatments. Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) with 177Lu-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:
A narrative literature review was conducted using the PubMed database to identify relevant studies published up to January 2026. This review summarizes preclinical and clinical evidence on the immunomodulatory effects of PSMA-targeted RLT. We discuss how 177Lu-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.
Insights
Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) shows promise in modulating the tumor immune microenvironment for metastatic castration-resistant prostate cancer (mCRPC). Further research into biomarkers and combination strategies is needed for optimal clinical benefit.
Area of Science:
- Oncology
- Radiopharmaceutical Therapy
- Immunotherapy
Background:
- Metastatic castration-resistant prostate cancer (mCRPC) presents significant therapeutic challenges.
- Advances in systemic treatments offer limited efficacy for many patients.
- Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) with 177Lu-PSMA-617 is an emerging treatment strategy.
Purpose of the Study:
- To review preclinical and clinical evidence on the immunomodulatory effects of PSMA-targeted RLT.
- To explore how 177Lu-PSMA-617 impacts immune cells and the tumor microenvironment.
- To examine the role of alternative radioligands and targeted agents.
Main Methods:
- A narrative literature review of studies up to January 2026.
- Utilized the PubMed database for study identification.
- Synthesized evidence on immunomodulatory effects, cell death induction, and microenvironmental interactions.
Main Results:
- 177Lu-PSMA-617 influences immune cell populations and induces immunogenic cell death.
- The therapy interacts with tumor microenvironmental factors like hypoxia, vascularization, and PSMA heterogeneity.
- Alternative radioligands (alpha-emitters, fibroblast activation protein-targeted agents) were also considered.
Conclusions:
- PSMA-targeted RLT shows potential as an immune-priming strategy in mCRPC.
- Clinical impact is currently limited by tumor and microenvironmental heterogeneity.
- Biomarker selection, dosimetry optimization, and combination with immunotherapy are crucial for maximizing clinical benefit.
