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     The image is immunohistochemistry of paraffin-embedded Human ovarian cancer tissue using P08688(SEMA4D Antibody) at dilution 1/40. (Original magnification: ×200)    

  
  

Semaphorin 4D (SEMA4D), also known as CD100. is a transmembrane glycoprotein belonging to the semaphorin family, initially recognized for its role in axonal guidance and immune regulation. It interacts with receptors such as Plexin-B1 and CD72. modulating cell migration, angiogenesis, and immune synapse formation. Dysregulated SEMA4D signaling is implicated in cancer progression, autoimmune disorders, and neurodegenerative diseases. In tumors, SEMA4D promotes immunosuppression by recruiting myeloid-derived suppressor cells (MDSCs) and inhibiting T-cell infiltration, while also stimulating angiogenesis and metastasis. In autoimmune conditions like multiple sclerosis or rheumatoid arthritis, SEMA4D contributes to pathogenic inflammation by activating immune cells.

SEMA4D-targeting antibodies have emerged as therapeutic agents to block these pathways. Preclinical studies show that anti-SEMA4D antibodies enhance antitumor immunity by reducing immunosuppressive cell infiltration and promoting cytotoxic T-cell activity. Concurrently, they mitigate autoimmune inflammation by interrupting SEMA4D-CD72 interactions critical for B-cell activation. Clinical trials in solid tumors and hematologic malignancies (e.g., prostate cancer, lymphoma) have demonstrated tolerability and preliminary efficacy, with some cases showing reduced tumor growth or stabilized disease. In autoimmune models, anti-SEMA4D therapy reduced demyelination and joint damage. Engineered to minimize immunogenicity, these antibodies often employ humanized frameworks. While long-term safety and efficacy remain under investigation, SEMA4D antibodies represent a dual-purpose strategy bridging oncology and immunology through microenvironment modulation.