Abstract
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).
Highlights
During the past decade, the development of immunotherapy (IO) has led to a dramatic improvement in the treatment of solid tumours
Many other immune agents were developed and are under clinical evaluation, either as single agents [1] or in combination with other immunotherapies, radiotherapy [2] or chemotherapy [3]. This huge effort is due to the knowledge that there are many immune escape mechanisms, frequently redundant, which explains why many patients do not benefit from IO, as recently reviewed [4,5]
We were able to identify cut-off values for IL-2 (0.055 pg/mL; Area Under the Curve (AUC): 0.193; 95% CI: 0.009–0.377; p = 0.013), IL-8 (10.75 pg/mL; AUC: 0.860; 95% CI: 0.701–1.000; p = 0.003) and CCL-2 (207.5 pg/mL; AUC: 0.848; 95% CI: 0.693–1.000; p = 0.005)
Summary
The development of immunotherapy (IO) has led to a dramatic improvement in the treatment of solid tumours. Axis inhibitors have produced spectacular results in cancers on which historically conventional anticancer therapies have limited impact, including malignant melanoma and lung cancer. Following these early successes, many other immune agents were developed and are under clinical evaluation, either as single agents [1] or in combination with other immunotherapies, radiotherapy [2] or chemotherapy [3]. Many other immune agents were developed and are under clinical evaluation, either as single agents [1] or in combination with other immunotherapies, radiotherapy [2] or chemotherapy [3] This huge effort is due to the knowledge that there are many immune escape mechanisms, frequently redundant, which explains why many patients do not benefit from IO, as recently reviewed [4,5]. IO has shown various levels of activity have been observed in most solid tumours, and this observation supports the hypothesis that the activity of IO is at least in part unrelated to the tumour type and is due to the modulation of the immune system rather than to a direct antitumour activity.
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