癌症骨转移免疫微环境的研究进展与治疗新策略OA

Cancer bone metastasis is a common and lethal complication of advanced solid tumors including breast,prostate,and lung cancers,severely impacting patients'quality of life and survival outcomes.The bone metastasis microenvironment(BME)is characterized by high heterogeneity and profound immunosuppression,which serves as a fertile soil for tumor colonization and growth,and is a key reason for the poor response to conventional therapies such as chemotherapy and radiotherapy,as well as immune checkpoint inhibitors.This review systematically elaborates on the composition and functional remodeling of key cellular components within the BME,including the transformation of myeloid cells from immune surveillance cells to tumor-promoting"accomplices",the functional exhaustion of T lymphocytes(especially CD8+T cells)and the immunosuppression mediated by regulatory T cells,as well as the pathological reprogramming of bone-resident cells such as osteoclasts,osteocytes,and osteoblasts under the influence of tumor cells.The review highlights the intricate interaction networks among these cells and unveils the pivotal roles of key signaling axes,DKK1/CHI3L3,osteopontin,and TIGIT/PD-1,in mediating CD8+T cell dysfunction and facilitating local and systemic immune evasion.Based on this,this article comprehensively summarizes the emerging therapeutic strategies for this complex microenvironment,mainly including:targeting specific subsets of immune cells to reverse immunosuppression,combining multiple immune checkpoint blockades,intervening in the pathological behaviors of bone resident cells,as well as cutting-edge technical platforms such as bone-targeted drug delivery systems based on nanotechnology and engineered cell therapies.By systematically synthesizing current research advances,this review aims to provide a solid theoretical foundation and forward-looking directions for deepening the understanding of the immunology of cancer bone metastasis and developing effective and precise treatment strategies.