CD47/SIRP alpha axis: bridging innate and adaptive immunity

Duijn, A. van; Burg, S.H. van der; Scheeren, F.A.

doi:doi:10.1136/jitc-2022-004589

Myeloid immune cells are frequently present in the tumor environment, and although they can positively contribute to tumor control they often negatively impact anticancer immune responses. One way of inhibiting the positive contributions of myeloid cells is by signaling through the cluster of differentiation 47 (CD47)/signal regulatory protein alpha (SIRP alpha) axis. The SIRP alpha receptor is expressed on myeloid cells and is an inhibitory immune receptor that, upon binding to CD47 protein, delivers a 'don't eat me' signal. As CD47 is often overexpressed on cancer cells, treatments targeting CD47/SIRP alpha have been under active investigation and are currently being tested in clinical settings. Interestingly, the CD47/SIRP alpha axis is also involved in T cell-mediated antitumor responses. In this perspective we provide an overview of recent studies showing how therapeutic blockade of the CD47/SIRP alpha axis improves the adaptive immune response. Furthermore, we discuss the...Show moreMyeloid immune cells are frequently present in the tumor environment, and although they can positively contribute to tumor control they often negatively impact anticancer immune responses. One way of inhibiting the positive contributions of myeloid cells is by signaling through the cluster of differentiation 47 (CD47)/signal regulatory protein alpha (SIRP alpha) axis. The SIRP alpha receptor is expressed on myeloid cells and is an inhibitory immune receptor that, upon binding to CD47 protein, delivers a 'don't eat me' signal. As CD47 is often overexpressed on cancer cells, treatments targeting CD47/SIRP alpha have been under active investigation and are currently being tested in clinical settings. Interestingly, the CD47/SIRP alpha axis is also involved in T cell-mediated antitumor responses. In this perspective we provide an overview of recent studies showing how therapeutic blockade of the CD47/SIRP alpha axis improves the adaptive immune response. Furthermore, we discuss the interconnection between the myeloid CD47/SIRP alpha axis and adaptive T cell responses as well as the potential therapeutic role of the CD47/SIRP alpha axis in tumors with acquired resistance to the classic immunotherapy through major histocompatibility complex downregulation. Altogether this review provides a profound insight for the optimal exploitation of CD47/SIRP alpha immune checkpoint therapy.Show less

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CD47/SIRP alpha axis: bridging innate and adaptive immunity