Figure 1.

Potential pathological mechanisms underlying neurological immune-related toxicities (NirAEs). A: Hypothesis under ICI. (1) ICIs may induce Tregs reduction and shift the balance towards immune tolerance loss and immune toxicity development (2) The similarity between a neoantigen and a self-antigen might induce T- or B-autoreactive cells wrongly directed against self-antigens (molecular-mimicry) (3) Cytotoxic CD8+ T-cells evoke tumor cell death but also non-transformed bystander cells death. The antigens released by both types of cells (antigen spreading) might be ingested and processed by antigen-presenting cells (APCs) priming new T- or B-cells leading to a autoimmunity reaction (4) PD-1 and CTLA-4 antibodies could recognize their target molecules expressed by non-hematopoietic cells, like in the nervous system, and induce a local injury through antibodies or T-cell cytotoxicity mechanisms. Modified from Vilariño N et al. 2020 [127].