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共刺激分子CD40/TNFRSF5隶属肿瘤坏死因子受体超家族，在机体固有免疫应答及适应性免疫应答中均发挥关键作用。CD40生理性表达于专职性抗原提呈细胞、内皮细胞等细胞表面，是T细胞表面CD40L分子的天然糖蛋白受体。CD40-CD40L信号通路的激活参与T淋巴细胞活化、抗体类别转换、抗原提呈细胞激活等一系列免疫相关生物学过程。除免疫细胞等生理性表达外，CD40在血源性及上皮源性恶性肿瘤细胞表面亦存在表达，并通过直接影响肿瘤细胞或间接干预肿瘤微环境参与肿瘤的发生、发展。大量研究表明，CD40激动型抗体可能通过激活宿主抗肿瘤免疫应答或直接促进CD40肿瘤细胞凋亡等途径正向干预实体肿瘤进展，提示CD40可能作为有效的肿瘤免疫治疗靶点。现对CD40分子在肿瘤发生、发展中的生物学作用及CD40-CD40L通路在肿瘤免疫治疗中的应用进展及存在问题予以综述。“,”Co-stimulator CD40/TNFRSF5 belongs to tumor necrosis factor receptors superfamily, which plays a key role in innate and adaptive immune responses.CD40 is a natural glycoprotein receptor of CD40L molecule on T cell surface, which is physiologically expressed on the surface of professional antigen presenting cells and endothelial cells.Activation of CD40-CD40L signaling pathway is involved in a series of immune-associated biological processes such as T lymphocyte activation, antibody class switching and antigen presenting cell activation.In addition to the physiological expression of immune cells, CD40 is also expressed on the surface of hematogenous and epithelial malignant tumors.CD40 is involved in the tumorigenesis and tumor development by directly influencing tumor cells or indirectly regulating tumor microenvironment.Most studies have shown that CD40 agonistic antibody may positively interfere with the progress of solid tumors by activating host anti-tumor immune response or directly promoting apoptosis of CD40 positive tumor cells, suggesting that CD40 may be an effective target for tumor immunotherapy.Here, we review the biological role of CD40 in tumorigenesis and development, and the progress in application and problems of CD40-CD40L pathway in cancer immunotherapy.