The CD276 gene, also known as B7-H3, encodes a type I transmembrane glycoprotein that belongs to the B7 family of immune checkpoint regulators ^[1]. Characterized by its limited expression in most normal human tissues, CD276 is frequently observed to be upregulated in a diverse range of human malignancies and within their associated tumor microenvironments, as well as on specific immune cell populations including antigen-presenting cells ^[2]. The encoded protein functions as a context-dependent modulator of T cell responses, exhibiting both co-stimulatory and co-inhibitory activities that influence T cell activation, proliferation, and cytokine production ^[3]. Expressed on tumor cells, antigen-presenting cells, and endothelial cells within the tumor vasculature, aberrant expression of CD276 has been strongly implicated in promoting tumor progression, metastasis, and the evasion of anti-tumor immunity, thereby positioning it as a compelling target for therapeutic intervention in oncology ^[4]. The B6-hB7-H3 (hCD276) mouse is a humanized model constructed by replacing the sequence of the mouse Cd276 endogenous extracellular domain in situ with the corresponding extracellular domain from the human CD276. The murine signal peptide was preserved. The B6-hB7-H3 (hCD276) mice can be used for the study of the pathogenesis of various cancers such as breast cancer, glioblastoma, and non-small cell lung cancer, as well as for CD276-targeted drug development.