Basal level and behaviour of cytokines in a randomized outpatient trial comparing chemotherapy and biochemotherapy in metastatic melanoma

Abstract

Cytokines play a crucial role in the host's immune response. In melanoma patients, cytokine profiles seems to be related to the clinical course and their imbalance could be associated to tumour progression. Thus, we studied a panel of baseline cytokines and their behaviour during treatment in order to verify their correlation with clinical outcomes. Interleukin-6, interleukin-8, interleukin-10, interleukin-12 and soluble receptor of interleukin-2 were evaluated in 90 out of 176 metastatic melanoma patients enrolled in a phase III study comparing chemotherapy and biochemotherapy. We divided patients into three different groups according to their own cytokine levels (low, intermediate and high) and then we correlated these groups with some clinical features. We also monitored the cytokines during the treatment in a subgroup of 37 patients. In univariate analysis, higher values of interleukin-6 (P = 0.005), soluble receptor of interleukin-2 (P = 0.001) and interleukin-12 (P = 0.010) were correlated with a worse survival. Conversely, interleukin-8 was unable to discriminate patients with different prognoses, and interleukin-10 was undetectable in the majority of patients. In multivariate analysis, only soluble receptor of interleukin-2 maintained its independent role in survival. The impact of baseline cytokines on response was insignificant. Regarding the behaviours of cytokines during treatment, the most remarkable aspect was a progressive increase of interleukin-12 and soluble receptor of interleukin-2 in patients with a better survival. In our metastatic melanoma patients, higher basal levels of interleukin-6, interleukin-12 and soluble receptor of interleukin-2 were associated with a worse survival. In contrast, a progressive increase of interleukin-12 and soluble receptor of interleukin-2 was observed during treatment in patients with a better survival.

Cytokine patterns in cancer patients: A review of the correlation between interleukin 6 and prognosis

“…Soft tissue sarcoma In 1 out of 1 series 149 17. Malignant melanoma In 5 out of 6 series 150-154 66 18. Classical Hodgkin's lymphoma In 1 out of 1 series 155 19 Diffuse large cell lymphoma In 2 out of 2 series 156,157 20.…”

“… 150 17 Metastatic melanoma 44 4.9 4.5 Guida et al. 151 18 Metastatic melanoma 25 16 7.3 Mouawad et al. 152 19 Metastatic melanoma 35 19 7.9 Soubrane et al.…”

Immune Parameters in The Prognosis and Therapy Monitoring of Cutaneous Melanoma Patients: Experience, Role, and Limitations

“…When we applied for IL-6 the 10 pg/mL cutoff value that was obtained from the first quartile of the values registered at first presentation in all patients, a clear correspondence of IL-6 level with survival appeared (Figure 14). A study published by the Italian Melanoma Intergroup evaluating chemotherapy versus biochemotherapy showed that higher values of IL-6 correlated with a worse survival [39]. An experimental mouse model has demonstrated that IL-6 is involved in both the development and progression of skin melanoma [40].…”

Serum Interleukin-8 Reflects Tumor Burden and Treatment Response across Malignancies of Multiple Tissue Origins

“…Although this fact may be explained by tumor burden, a contribution by a direct pathogenic role of IL8 cannot be excluded, because IL8 is involved in tumor vascularization (5,45) and chemotactically disorients migration of immune cells (12). Guida and colleagues (46) have reported that IL8 was unrelated with prognoses in patients with metastatic melanoma, even though the group with the highest levels of IL8 presented the lowest median OS. Other groups have reported lack of association of IL8 and prognosis (34,(47)(48)(49).…”