CELL INTELLIGENCE · 肿瘤细胞治疗研究

BACKGROUND: Despite the success of immunotherapy in other malignancies, castration-resistant prostate cancer (CRPC) remains a formidable challenge due to its immunosuppressive "cold" tumor microenvironment. This environment is characterized by low tumor mutational burden, sparse T-cell infiltration, and the dominance of immunosuppressive factors. This review aims to systematically examine recent advances, current challenges, and future directions in immunotherapy for CRPC, offering novel therapeutic perspectives for this lethal disease with currently limited treatment options. METHODS AND RESULTS: We reviewed the research results of immunotherapy for CRPC in PubMed, Web of Science and CNKI literature from 2020 to 2025 and found that significant clinical progress has been made in this field: 5 vaccine trials, 3 immune checkpoint inhibitor trials, 20 combination therapy trials ( 2 drugs), and 7 targeted drug trials. Preliminary efficacy was observed in new approaches such as bispecific antibodies (for example, Xaluritamig achieved a 59% PSA50 response), PSCA-CAR T, and oncolytic viruses (Ad5 PSA/MUC-1/brachyury). Basic research has identified four targeted resistance mechanisms (such as AR-LLT1, Pygo2, HnRNP L) and one nanoparticle mediated triple therapy (CM-AMS@AD NPs integrated photothermal/chemotherapy/immunotherapy), which can enhance cytotoxic T cell infiltration and inhibit preclinical CRPC growth. CONCLUSIONS: These findings demonstrate the significant potential of immunotherapy in treating CRPC, but treatment regimens require further optimization and validation of long-term survival benefits through Phase III clinical trials.