Abstract：
:Tumors routinely attract and co-opt macrophages to promote their growth, angiogenesis, and metastasis. Macrophages are also the key effector cell for mAb therapies. Here we report that the tumor microenvironment creates an immunosuppressive signature on tumor-associated macrophages (TAM), which favors expression of inhibitory rather than activating Fcγ receptors (FcγR), thereby limiting the efficacy of mAb immunotherapy. We assessed a panel of TLR and STING agonists (a) for their ability to reprogram macrophages to a state optimal for mAb immunotherapy. Both STINGa and TLRa induced cytokine release, modulated FcγR expression, and augmented mAb-mediated tumor cell phagocytosis in vitro However, only STINGa reversed the suppressive FcγR profile in vivo, providing strong adjuvant effects to anti-CD20 mAb in murine models of lymphoma. Potent adjuvants like STINGa, which can improve FcγR activatory:inhibitory (A:I) ratios on TAM, are appealing candidates to reprogram TAM and curb tumor-mediated immunosuppression, thereby empowering mAb efficacy. Cancer Res; 77(13); 3619-31. ©2017 AACR.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Dahal LN,Dou L,Hussain K,Liu R,Earley A,Cox KL,Murinello S,Tracy I,Forconi F,Steele AJ,Duriez PJ,Gomez-Nicola D,Teeling JL,Glennie MJ,Cragg MS,Beers SAdoi
10.1158/0008-5472.CAN-16-2784subject
Has Abstractpub_date
2017-07-01 00:00:00pages
3619-3631issue
13eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-16-2784journal_volume
77pub_type
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