The role of the complement system in the response to cytotoxic therapy

The complement system is increasingly recognised as a key player in tumour progression and response to cancer treatment. Cytotoxic therapies, including chemo- and radiotherapy are standard-of-care for the majority of cancer patients. Cytotoxics have been found to alter the expression of complement system proteins and activation of components. Many recent reports highlight the role of local dysregulation of complement proteins in the tumour microenvironment and how targeting such dysregulation can have either anti- or pro-tumoricidal effects depending on several factors including treatment scheduling, the tumour type and its microenvironment characteristics. This review will explore the complex effects of cytotoxic therapy on complement regulation and what lessons can be learnt to identify the most effective way to therapeutically modulate complement system proteins for cancer therapy.