分泌性磷酸化蛋白1在前列腺癌免疫治疗中的机制及研究进展

Mechanisms and Research Advances of Secreted Phosphoprotein 1 in the Immunotherapy of Prostate Cancer

摘要: 前列腺癌是男性最常见的恶性肿瘤之一，传统治疗方法包括手术、化疗、放疗及雄激素剥夺治疗等，患者初始可获益，但绝大多数终将进展为去势抵抗性前列腺癌，面临耐药难题。由于前列腺癌特殊的免疫逃逸机制及肿瘤微环境显著的免疫抑制特征，免疫治疗收效甚微，如何破解“冷肿瘤”困境成为关键。分泌性磷酸化蛋白1 (SPP1)作为一种多功能磷酸化糖蛋白，被认为是极具前景的治疗靶点，其通过调节先天性和适应性免疫系统，促进肿瘤血管生成、侵袭、转移和免疫抑制。本文针对SPP1的生物学特性、SPP1在前列腺癌中的作用、SPP1在前列腺癌免疫治疗中的新策略与生物标志物潜能等3个方面进行论述，旨在揭示SPP1影响前列腺癌免疫治疗的科学内涵，为临床转化提供理论支撑与参考。

Abstract: Prostate cancer remains one of the most prevalent malignancies affecting men worldwide. Although conventional therapeutic approaches-such as surgical resection, chemotherapy, radiotherapy, and androgen deprivation therapy (ADT)-often yield initial clinical responses, the majority of patients eventually progress to castration-resistant prostate cancer (CRPC), highlighting the persistent challenge of treatment resistance. Immunotherapeutic strategies have demonstrated limited success in prostate cancer, largely due to intrinsic immune evasion mechanisms and the establishment of a profoundly immunosuppressive tumor microenvironment (TME). As such, transforming the immunologically “cold” phenotype of prostate tumors into an immunoresponsive state represents a pivotal therapeutic goal. Secreted Phosphoprotein 1 (SPP1), also known as osteopontin, is a multifunctional phosphorylated glycoprotein that plays a central role in modulating both innate and adaptive immune responses, while simultaneously promoting tumor angiogenesis, invasion, metastasis, and immunosuppression. This review provides a comprehensive analysis of SPP1 from three perspectives: its molecular and biological characteristics, its pathogenic contributions to prostate cancer progression, and its potential utility as a predictive biomarker and therapeutic target in immunotherapy. By elucidating the mechanistic underpinnings of SPP1-mediated immune regulation in prostate cancer, this work aims to provide a robust theoretical framework to support future clinical translation.