Cytokine-based immunotherapy in hematolymphoid malignancies

Cytokines regulate both innate and adaptive immunity, thus bridging these two types of immune response. Initially explored as standalone cancer therapies, their use was hindered by the unfavorable pharmacokinetic profiles of recombinant molecules and the competition from newer, more promising immunotherapies. However, with the advent of bioengineered cytokines featuring extended half-lives and reduced off-target effects, their therapeutic potential is being re-evaluated, especially in combination with monoclonal antibodies, immune checkpoint inhibitors, cancer vaccines, and advanced cellular therapies. Regarding cellular therapies, cytokines can be used to enhance the ex vivo expansion of therapeutic bioproducts or improve their in vivo persistence and function. In the context of allogeneic hematopoietic stem cell transplantation, cytokines may support immune reconstitution, thereby reducing the risk of serious infections and disease recurrence. The immunomodulatory role of cytokines is particularly relevant in hematolymphoid malignancies, given the rising incidence of these conditions and the increasing cumulative exposure to various classes of chemotherapeutic agents. Also, this happens in a context where there is a decline in immune function, particularly relevant in older adults and in those with other chronic illnesses. In this review, we examine recent advances in cytokine-based therapies for hematological malignancies, both as monotherapy and in combination with chemotherapeutic agents, immunomodulatory drugs, or advanced cellular therapies.