| First Author | Dahal LN | Year | 2017 |
| Journal | Cancer Res | Volume | 77 |
| Issue | 13 | Pages | 3619-3631 |
| PubMed ID | 28512240 | Mgi Jnum | J:243117 |
| Mgi Id | MGI:5907747 | Doi | 10.1158/0008-5472.CAN-16-2784 |
| Citation | Dahal LN, et al. (2017) STING Activation Reverses Lymphoma-Mediated Resistance to Antibody Immunotherapy. Cancer Res 77(13):3619-3631 |
| abstractText | 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 Fcgamma receptors (FcgammaR), 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 FcgammaR expression, and augmented mAb-mediated tumor cell phagocytosis in vitro However, only STINGa reversed the suppressive FcgammaR profile in vivo, providing strong adjuvant effects to anti-CD20 mAb in murine models of lymphoma. Potent adjuvants like STINGa, which can improve FcgammaR 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. (c)2017 AACR. |
