Abstract

Macrophages that have differentiated through interaction with tumour cells have been shown to play a key role in exerting local immunosuppression and promoting tumour metastasis, neoplastic invasion of ectopic tissue and angiogenesis. Macrophages are also the key effector cells for direct targeting monoclonal antibody (mAb) therapies, engaged by their Fc gamma receptors (FcγR). We have identified that the tumour microenvironment drives an immunosuppressive signature on tumour associated macrophages (TAM) characterised by a low FcγR activatory:inhibitory (A:I) expression ratio, resulting in ineffective mAb immunotherapy. Here we show that STING agonists are able to overcome this tumour driven immunosuppression effectively reversing the TAM inhibitory FcγR profile and providing strong adjuvant effects to antibody therapy.