Cytokine profiling of end stage cancer patients treated with immunotherapy

Published data suggest that immunotherapy plays a role even in patients with very advanced tumours. We investigated the immune profile of end‐stage cancer patients treated with immunotherapy to identify changes induced by treatment. Breast, colon, renal and prostate cancer patients were eligible. Treatment consisted of metronomic cyclophosphamide, low‐dose interleukin‐2 (IL‐2) and a single radiation shot. A panel of 16 cytokines was assessed using automated ELISA before treatment (T0), after radiation (RT; T1), at cycle 2 (T2) and at disease progression (TPD). Receiving operating characteristic (ROC) analysis was used to identify cytokine cut‐off related to overall survival (OS). Principal component analysis (PCA) was used to identify the immune profile correlating better with OS and progression‐free survival. Twenty‐three patients were enrolled. High IL‐2, low IL‐8 and CCL‐2 correlated with OS. The PCA identified a cluster of patients, with high IL‐2, IL‐12 and IFN‐γ levels at T0 having longer PFS and OS. In all cohorts, IL‐2 and IL‐5 increased from T0 to T2; a higher CCL‐4 level compared to T2 and a higher IL‐8 level compared to T0 were found at TPD. The progressive increase of the IL‐10 level during treatment negatively correlated with OS. Our data suggested that baseline cytokine levels may predict patients’ outcome and that the treatment may affect their kinetic even in end‐stage patients. Cytokine profiling of end‐stage patients might offer a tool for medical decisions (EUDRACT: 2016‐ 000578‐39).