Despite the success in various other cancer types, there are no approved immune therapies for ovarian cancer, as response of ovarian cancer to immunotherapies thus far have been modest. Early studies of single agent anti-PD-1 antibodies in patients with platinum-resistant or recurrent ovarian cancer demonstrated response rates of between 8–15%. Combination strategies combining PD-1 or PD-L1 antibodies with anti-CTLA-4 antibodies have demonstrated slightly higher response rates of over 30%. Additional studies including chemotherapy in combination with immune checkpoint inhibitors (ICI) have shown no additional benefit of addition of ICI to traditional chemotherapy regimens. We argue that outside of a clinical trial, there is no evidence to support routine usage of ICIs in EOC, even in a heavily pretreated platinum-resistant setting, although we are hopeful that biomarkers that may predict response to ICIs in ovarian cancer may be identified in the future. Lastly, we anticipate that emerging approaches in ovarian cancer immunotherapy such as novel ICI combinations, antibody-drug conjugates, bispecific antibodies, cytokines, and adoptive cell therapies will prove to be successful and look forward to the results of these studies.

In this chapter we review the CNS syndromes mediated by autoimmune or inflammatory mechanisms in patients with cancer. Paraneoplastic neurological syndromes (PNS) are considered to be immune-mediated disorders against proteins expressed by the tumour and nervous system. The autoimmune hypothesis is supported by the presence in serum and CSF of antibodies against neural proteins that are also expressed in the tumour. Less frequently the tumour does not express neuronal proteins but predisposes to immune dysregulation and autoimmune mechanisms. Novel cancer therapies that enhance anti-tumour immune responses frequently cause inflammatory CNS disorders. Immune checkpoint inhibitors have been associated with a wide range of immune-related adverse effects, including an increased incidence of PNS. Another type of cancer therapy is based on the use of T cells genetically engineered to express chimeric antigen receptors (CARs) that recognize molecules present on the surface of tumour cells. CAR T cell therapy can cause severe, potentially lethal, encephalopathy syndromes mediated by massive release of cytokines instead of autoimmune mechanisms. Post-transplant autoimmune encephalitis are rare disorders that mostly occur after allogeneic haematopoietic stem cell transplantation. They are related to graft versus host disease and, sometimes, they associate with antibodies against neuronal surface antigens.

Some types of autoimmune encephalitis associate with distinct HLA haplotypes that likely predispose to the disease (e.g., anti-LGI1 encephalitis or anti-IgLON5 disease). In other instances the autoimmune mechanisms are triggered by tumours that express the neuronal antigen (e.g., small-cell lung cancer and anti-GABAbR encephalitis), or tumours that cause an immune dysregulation (thymoma and anti-GABAaR or anti-AMPAR encephalitis), or viral encephalitis that lead to neuronal destruction and release of antigens (e.g., herpes simplex encephalitis triggering autoimmune encephalitis with NMDAR or GABAaR antibodies). In most autoimmune encephalitis the pathogenic antibodies are IgG1 and cause symptoms by internalization of the target antigen (anti-NMDAR encephalitis) or antibody-mediated complement activation and cellular injury (aquaporin 4 antibodies in neuromyelitis optica spectrum disorders). Direct functional blocking of the antigen has been demonstrated for glycine receptor antibodies and probably GABAbR antibodies. Some autoimmune encephalitis (e.g., anti-LGI1 or CASPR2 encephalitis, anti-IgLON5 disease) associate with predominant IgG4 antibodies that disrupt normal protein–protein interactions. Confirmation of antibody pathogenicity requires that in passive transfer experiments of patients’ antibodies to animals, the antibodies bind to the target neural antigen, alter the structure or function of the antigen, and result in clinical symptoms.

In this chapter we review the CNS syndromes mediated by autoimmune or inflammatory mechanisms in patients with cancer. Paraneoplastic neurological syndromes (PNS) are considered to be immune-mediated disorders against proteins expressed by the tumour and nervous system. The autoimmune hypothesis is supported by the presence in serum and CSF of antibodies against neural proteins that are also expressed in the tumour. Less frequently the tumour does not express neuronal proteins but predisposes to immune dysregulation and autoimmune mechanisms. Novel cancer therapies that enhance anti-tumour immune responses frequently cause inflammatory CNS disorders. Immune checkpoint inhibitors have been associated with a wide range of immune-related adverse effects, including an increased incidence of PNS. Another type of cancer therapy is based on the use of T cells genetically engineered to express chimeric antigen receptors (CARs) that recognize molecules present on the surface of tumour cells. CAR T cell therapy can cause severe, potentially lethal, encephalopathy syndromes mediated by massive release of cytokines instead of autoimmune mechanisms. Post-transplant autoimmune encephalitis are rare disorders that mostly occur after allogeneic haematopoietic stem cell transplantation. They are related to graft versus host disease and, sometimes, they associate with antibodies against neuronal surface antigens.