Fig. 6
From: Blood–brain barrier permeable nano immunoconjugates induce local immune responses for glioma therapy
Proposed mechanism of local brain immune activation by NIC treatment. a The proposed mechanism of synergistic treatment with a-CTLA-4 and a-PD-1 mAbs when they cross BBB as part of a nano immunodrug. (1) a-PD-1 initiates central pathway inhibition with cancer cell attack; (2) a-PD-1 activates cytotoxic T lymphocytes; and (3) a-CTLA-4 provides local inhibition of Treg. In addition, activated macrophages (MΦ) and NK cells also contribute to tumor cell elimination. IL interleukin; IFN interferon. b Ex vivo study of M1 MΦ by immunostaining for iNOS (arrows) demonstrates their increased numbers in the brain tumors after combined NIC treatment as compared to PBS or a combination of free antibodies. Data are mean ± SEM. **p < 0.01; ****p < 0.0001 (ANOVA with Sidak’s posttest)
