Intratumoral administration of cGAMP transiently accumulates potent macrophages for anti-tumor immunity at a mouse tumor site

We describe here our finding th at a CD45+ CD11bmid Ly6C+ cell subset transiently accumulated in mouse tumor microenvironment of 4T1 breast cancer, squamous cell carcinomas, CT26 colon cancer, or B16F10 melanoma tissue after intratumoral injection of cGAMP. The accumulated cells displayed a macrophage (M ) phenotype since the cells were positive for F4/80 and MHC class II and negative for Ly6G. Intratumoral cGAMP treatment did not induce M φ accumulation in STING-deficient mice. Depletion of CD8+ T cell using anti-CD8 mAb impaired the anti-tumor effects of cGAMP treatment. Depletion of the M φ using clodronate liposomes impaired the anti-tumor effects of cGAMP treatment. Functional analysis indicated that the STING-triggered tumor-migrating Mφ exhibited phagocytic activity, production of tumor necrosis factor alpha TNFα), and high expression levels of T cell-recruiting chemokines,Cxcl10 andCxcl11, IFN-induced molecules,MX dynamin-like GTPase 1 (Mx1) and2 ′-5′ oligoadenylate synthetase-like 1 (Oasl1),nitric oxide synthase 2 (Nos2), andinterferon beta 1 (Ifnb1). These results indicate that the STING-triggered tumor-migrating M φ participate in the anti-tumor effects of STING-activating compounds.
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research