CD 47‐signal regulatory protein α signaling system and its application to cancer immunotherapy

Tumor cells evade immune surveillance through direct or indirect interactions with various types of immune cell, with much recent attention being focused on modifying immune cell responses as the basis for the development of new cancer treatments. Signal regulatory protein α ( SIRP α) and CD 47 are both transmembrane proteins that interact with each other and constitute a cell‐cell communication system. SIRP α is particularly abundant in myeloid cells such as macrophages and dendritic cells, whereas CD 47 is expressed ubiquitously and its expression level is elevated in cancer cells. Recent studies have shown that blockade of CD 47‐ SIRP α interaction enhances the phagocytic activity of phagocytes such as macrophages toward tumor cells in vitro as well as resulting in the efficient eradication of tumor cells in a variety of xenograft or syngeneic mouse models of cancer. Moreover, CD 47 blockade has been shown to promote the stimulation of tumor‐specific cytotoxic T cells by macrophages or dendritic cells. Biological agents, such as Abs and recombinant proteins, that target human CD 47 or SIRP α have been developed and are being tested in preclinical models of human cancer or in clinical trials with cancer patients. Preclinical studies have also suggested that CD 47 or SIRP α blockade may have a synergistic antitumor effect in combination with immune checkpoint inhibitors that target the adaptive immune system. Targeting of the CD 47‐ SIRP α signaling system is thus a promising strategy for cancer treatment based on modulation of both innate and acquired immune responses to tumor cells.