Figure 2.

Innate and adoptive immune responses in CNS tumors. Brain tumors induce the recruitment of myeloid and lymphoid cells. Brain-resident and recruited cell types exert different functions within tumor-associated inflammation. Brain resident microglia maintain functions associated to their role as the innate immune cell of the CNS including host defense and synaptic pruning while bone marrow derived macrophages are associated with antigen-presentation, immune suppression and wound healing/tumor promoting functions. TAM-BMDMs express high levels of checkpoint molecules including PD-L1 to inactivate T cells. Dendritic cells traffic between CNS tumors and the cervical lymph nodes to prime T cells against tumor neo-antigens. T cells receive activating signals through interactions of the T cell receptor with antigens presented on MHC molecules and co-stimulation through interactions with CD28 and CD80/CD86. DC express the checkpoint molecule CTLA-4 that binds to CD28 on T cells to prevent activation of auto-reactive T cells. It remains unclear to which extent DCs activate or inhibit cytotoxic T cell functions in CNS tumors. Cytotoxic T cell responses are further inhibited by aberrant expression of checkpoint molecules on tumor cells as well as the secretion of immune-suppressive cytokines by Tregs, astrocytes and neurons. Checkpoint inhibitors (Immune Checkpoint Blockade; ICB) that block CTLA-4, PD-1, or PD-L1 unleash T cell effector functions to induce cytotoxic activity against tumor cells.