Under normal physiological conditions, some types of phagocytes, such as macrophages, dendritic cells, and neutrophil granulocytes in our body play an important role in protecting our health by engulfing and digesting foreign substances, microbes, dead cells and cellular debris. They are working as brave soldiers. But every coin has two sides. These types of phagocytes are also dangerous due to the fact that they can be scavengers and engulf normal cells. 

The phagocytosis of cells relies on a balance between pro-phagocytic ("eat me") and anti-phagocytic ("don’t eat me") signals on the cell surface. Cluster of differentiation 47 (CD47), a member of the immunoglobulin superfamily, expresses on all cells. CD47 inhibits the phagocytosis of cells by binding to its receptor, namely, signal regulatory protein α (SIRPα), which is expressed on phagocytes. Lacking in CD47 erythrocytes, platelets and lymphohematopoetic cells will be rapidly cleared by macrophages. Abundant CD47 has also been observed on a variety of malignant cells, where elevated CD47 expression has predicted poor survival in individuals with cancer. 

Many researchers have made great efforts to study the therapeutic effects of anti-CD47 mAb over the years. However, how to use anti-CD47 mAb as a cancer therapy has not been demonstrated clearly. Recent studies in various preclinical xenografted models of human lymphoma have revealed that the therapeutic effects of anti-human CD47 were macrophage dependent. However, these studies employed xenografted human tumors in T cell-deficient mice. Therefore, these studies cannot evaluate the role of adaptive immunity in the effectiveness of anti-CD47 mAb. It remains unclear whether anti-CD47 monoclonal antibodies themselves can activate the adaptive immune response of the body.

In a new study published online by Nature Medicine on Sept. 1, entitled “CD47 Blockade Triggers T Cell–Mediated Destruction of Immunogenic Tumors,” LIU Xiaojuan of the Institute of Biophysics and Meng Xu of the University of Chicago, led by Prof. FU Yang-Xin, revealed that the therapeutic effect of antibody-mediated CD47 blockade in syngeneic tumor models largely depends on the activation of T cells. 

This study shows that the therapeutic effect of anti-CD47 mAb relies on a cytosolic DNA sensor, dendritic cells, type I/II interferons and CD8⁺ T cells and concludes that anti-CD47 mAb-mediated tumor rejection requires both innate and adaptive immune response. In addition, the researchers found that a timely combination of conventional chemotherapy with immunotherapy using anti-CD47 mAb can boost the host response and thus control tumor growth. 

Evaluating the research, international peer reviewers said, "Liu et al evaluate CD47 antibody blockade in a proper model and reveal strong evidence of dentritic cells dependent adaptive T cell immunity in contrast to a large body of high impact publications suggesting CD47 blockade drives mainly a macrophage-dependent phagocytic anti-tumor mechanism." They added that “the findings of this manuscript are therefore potentially of high impact” and “the data are very strong and clear.”. 

The study yields important information for designing new treatment using anti-CD47 mAbs and also stresses the importance of using immunocompetent hosts harboring a syngeneic tumor for future cancer studies. With the development of antibody therapeutics in cancer, monoclonal antibodies have entered the mainstream of cancer therapy. Also, with the beginning of human clinical trials of anti-human CD47 cancer therapy in 2014, these increasingly promising research results regarding anti-CD47 mAb will definitely give physicians indicators of how the treatment is working in patients.