Tumor Lysis Syndrome and Cytokine Storm: Two Sides of The Same Coin?

Author(s): Maria Saveria Rotundo and Roberto Verna

Cytokines are small proteins released by cells, which can act synergistically or antagonistically to enable cellular interactions through pleiotropy (one cytokine exhibits multiple functionalities) and redundancy (multiple cytokines exert overlapping activities). They act in concert with specific cytokine inhibitors and soluble cytokine receptors to regulate immune response and their role in inflammatory processes is widely recognized. During tumor lysis, secondary to cancer cell death, the release of cytokines may occur massively, and an amplified tumor immunogenicity, which allows to elicit immune activation pathways and trigger a greater immune antitumoral response, is observed. The present search was performed to identify the molecular mechanisms involved in the cytokine release during cell death. The emerging data suggests the possibility of modelling the tumor microenvironment, converting an immunologically "cold" tumor into a "hot" tumor, thanks to novel combination strategies of immunotherapy and immunogenic cell death inducers, aimed to trigger a tumor-targeted adaptive response against immune silencing. However, significant effort is required to prevent and early diagnose tumor lysis syndrome and cytokine release syndrome due to the potential for life-threatening metabolic and immune-related adverse events.