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- Key words: immunotherapy, dendritic cells, macrophages, CD47, SIRPα
- DOI : 10.1684/ito.2018.0139
- Page(s) : 229-34
- Published in: 2018
The success of immunotherapeutic treatments targeting checkpoints of adaptive immunity, particularly on T-cells (PD-1, PD-L1, CTLA-4), has led to the emergence and routine clinical use of new treatments in patients with advanced-stage cancers. Although impressive results have been reported for these new treatments in some patients, most patients remain non-responders and effectiveness is variable or even absent depending on the tumour type. The innate immune cells, especially myeloid cells, also play a key role in our immune system and their accumulation in the periphery and/or into the tumour has been identified as one of the most important immunological mechanisms for treatment resistance. SIRPa is a checkpoint for myeloid cells, initially identified as a negative regulator of macrophage phagocytosis and antigen cross-presentation by dendritic cells. The suppressive myeloid cells (TAM/MDSC) expressing SIRPa have an important role in the immunosuppression of the tumoural microenvironment by inhibiting the antitumoral effect of T cells and NK cells. Overexpression of the SIRPa ligand, CD47, by tumour cells is correlated with a poor clinical outcome. This article summarises the fundamental knowledge around the biology of SIRPa/CD47 interaction and describes the various therapeutic strategies which are currently in clinical development to block this inhibitor pathway in oncology.