Cytokines in hematopoietic cell transplantation and related cellular therapies

Cytokines are pleiotropic molecules involved in hematopoiesis, immune responses, infections, and inflammation. They play critical roles in hematopoietic cell transplantation (HCT) and immune effector cell (IEC) therapies, mediating both therapeutic and adverse effects. Thus, cytokines contribute to the immunopathology of graft-versus-host disease (GVHD), cytokine release syndrome (CRS), and immune effector cell-associated neurotoxicity syndrome (ICANS). This review examines cytokine functions in these contexts, their influence on engraftment and immune recovery post-transplantation, and their role in mediating toxicities. We focus on current and potential uses of cytokines to enhance engraftment and potentiate IEC therapies, as well as strategies to mitigate cytokine-mediated complications using cytokine blockers (e.g., tocilizumab, anakinra) and JAK inhibitors (e.g., ruxolitinib). We discuss new insights into GVHD physiology that have led to novel treatments, such as CSF1R blockade, which is effective in refractory chronic GVHD.