Purpose of ReviewImmune checkpoint immunotherapies (ICI) are now approved for over 20 types of cancer and there are almost 6000 ongoing clinical trials investigating immuno-modulators as cancer therapies. This review investigated the effect of monoclonal antibody-based immune checkpoint immunotherapies when combined with cytokine therapy. We reviewed published clinical trial results from 2005 to 2020 for studies that used approved monoclonal antibody ICI in combination with the cytokines. Studies that met the search criteria were assessed for treatment efficacy and immunological changes associated with treatment.Recent FindingICI often fails to result in improved clinical outcomes for patients and lasting protection from cancer recurrence. The use of pro-inflammatory cytokines alongside ICI has been shown to enhance the efficacy of these therapies in vitro and in animal studies. However, the results in human clinical trials are less clear and many clinical trials do not publish results at the end of the trial.SummaryA deeper understanding of the molecular interactions between cytokines, tumors, and immune cells is needed to improve overall ICI outcomes and design combination trials. Critical examination of the design and characteristics of previous clinical trials can provide insight into the lack of effective clinical translation for many immunotherapeutic drugs.