Circulating proteins as biomarkers of response to cancer immunotherapy (Review)

Immune checkpoint inhibitors (ICIs) have revolutionized cancer management; however, durable benefit is observed only in a minority of patients. To overcome the limitations of currently approved tumour tissue‑based biomarkers of response, several approaches based on liquid biopsy are currently being developed. Among them, circulating proteins, such as soluble immune checkpoint regulators, cytokines, chemokines, growth factors and cellular modulators, are being increasingly assessed by multiplex technologies that use a low volume of biofluids and offer rapid results. Serum/plasma programmed death‑ligand 1, cytotoxic t‑lymphocyte‑associated protein 4, T‑cell immunoglobulin and mucin‑domain containing‑3, lymphocyte activation gene‑3, interleukin (IL)‑6 and IL‑8 have emerged as potentially useful indicators of early response or resistance to ICIs, particularly when quantified during treatment. However, the optimal timing of on‑treatment blood sampling remains to be determined. The current review aimed to present the most important findings on the association between circulating proteins and response to ICIs in solid tumours, and to discuss the position of this biomarker class in the current landscape of biomarkers for ICI therapy.