The reinvigoration of anti-tumor T cells in response to immune checkpoint blockade (ICB) therapy is well established. Whether and how ICB therapy manipulates antibody-mediated immune response in cancer environments, however, remains elusive. Using tandem mass spectrometric analysis of modification of immunoglobulin G (IgG) from hepatoma tissues, we identified a role of ICB therapy in catalyzing IgG sialylation in the Fc region. Effector T cells triggered sialylation of IgG via an interferon (IFN)-γ-ST6Gal-I-dependent pathway. DC-SIGN+ macrophages represented the main target cells of sialylated IgG. Upon interacting with sialylated IgG, DC-SIGN stimulated Raf-1-elicited elevation of ATF3, which inactivated cGAS-STING pathway and eliminated subsequent type-I-IFN-triggered antitumorigenic immunity. Although enhanced IgG sialylation in tumors predicted improved therapeutic outcomes for patients receiving ICB therapy, impeding IgG sialylation augmented antitumorigenic T cell immunity after ICB therapy. Thus, targeting antibody-based negative feedback action of ICB therapy has potential for improving efficacy of cancer immunotherapies. Display omitted •ICB therapy catalyzes IgG sialylation in HCC that predicts an improved outcome•Effector T cells trigger sialylated IgG via IFN-γ-ST6Gal-I-dependent pathways•Sialylated IgG binding to DC-SIGN abrogates macrophage type I IFN production•Impeding IgG sialylation enhances antitumorigenic T cell immunity during ICB therapy Although immune checkpoint blockade (ICB) influence on T cells is well known, its impact on antibodies is less understood. Wu et al. show how ICB-elicited sialylation of IgG suppresses DC-SIGN-expressing macrophages in human hepatocellular carcinoma. Impeding IgG sialylation augments macrophage IFN-I responses and antitumorigenic T cell immunity during immunotherapy.