Immune-mediated side effects of cancer immunotherapies

Immunotherapies, such as allogeneic hematopoietic cell transplantation and infusion of chimeric antigen receptor T (CAR-T) cells have significantly extended our therapeutic armamentarium against several hematological malignancies. Blocking negative regulators of immunity with immune checkpoint inhibitors has significantly improved the survival of patients with mainly solid tumors. Despite their beneficial effects, these therapies are also associated with severe, immune-mediated side effects. Here, we discuss biological similarities and differences of acute graft-versus-host disease (GVHD), cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), immune effector cell-associated hemophagocytic lymphohistiocytosis like syndrome (IEC-HS), immune effector cell-associated hematotoxicity (ICAHT), local immune effector cell-associated toxicity syndrome (LICATS), and immune-related adverse events after immune checkpoint inhibition (irAEs). Recent data have led to a better understanding of the role of myeloid cells and T-cells, including tissue-resident T-cells, in the pathophysiology of GVHD, CAR-T-cell associated immunotoxicities and irAEs. Further, we summarize approved, currently evaluated and potential future therapies for immune-mediated toxicities of cancer immunotherapies. This review will help to understand how therapeutic strategies target communalities of different side effects to overcome immune-mediated side effects of cancer immunotherapies.