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English: Figure 1. Pathogenic mechanisms involved in neurological immune related adverse events triggered by immune checkpoint inhibitors. Tumor antigens released from necrotic tumor cells are captured, processed into peptides by antigen-presenting cells (APC) that present them on major histocompatibility complex (MHC) molecules to the naïve T-cells in the lymph nodes. The T-cell receptor (TCR) engages with MHC molecules on the APC. Co-stimulatory signals from the interaction between CD28 on T-cells and B7 (CD80/86) on the APC are necessary to activate a naïve T-cell. This results in activation of CD8 cytotoxic T-cells against tumor-specific antigens, and CD4 helper T-cells that will help activate B-cells that have engaged via their B-cell receptor their cognate antigen and push them into antibody-producing plasma cells (PC). There are also inhibitory signals, or immune checkpoints, that regulate T-cell activation. CTLA4 on T-cells competes with CD28 for B7 binding. The interaction between CTLA4 and B7 is an inhibitory signal for T-cells. CTLA4 blockade therefore leads to enhanced T-cell activation in the lymph node. CD8 cytotoxic T-cells and plasma cells travel to the tumor. PDL1 expressed by the antigen-specific T-cells binds to PD-L1 expressed by tumor cells, leading to an inhibitory signal. Blockade of PD1/PD-L1 leads to enhanced T-cell activation on a tissue level. CD8 cytotoxic T-cells and plasma cells also travel to the nervous system. CD8 cytotoxic T-cells directed against neural antigens (that are aberrantly expressed by the tumor) will cause direct cytotoxicity and cell death. Antibodies directed against cell-surface neural antigens (aberrantly expressed by the tumor) can cause cell damage via several different pathways: by complement activation or antibody dependent cellular cytotoxicity (ADCC), by antigen internalization (modulation), or by antigen blocking with interruption of its function. Reproduced with permission from Sechi and Zekeridou (35). Suggested mechanisms of neurological autoimmunity in the context of ICI treatment.