Circulating IL-6 is associated with disease progression in BRAFwt metastatic melanoma patients receiving anti-PD-1 therapy

Abstract

AimsDespite efficacy of anti-PD-1 blockade in treatment of metastatic melanoma (MM), many patients achieve rapid disease progression (DP). Therefore, the aim of this study is to better define biomarkers for DP by analysing levels of circulating cytokines TGF-β, IFN-γ, IL-6, IL-8 and IL-10 in MM patients prior to anti-PD-1 therapy.MethodsCytokine levels were evaluated before therapy with pembrolizumab in peripheral blood of BRAF wild-type (wt) MM patients by ELISA method.ResultsIn this study, we give pretherapy levels for circulating TGF-β, IFN-γ, IL-6, IL-8 and IL-10 in BRAFwt MM patients and analyse them according to metastasis stage (M1a+M1 b, M1c, M1d groups), lactate dehydrogenase (LDH) level and occurrence of DP. Increased IL-6 level was found in M1d group (central nervous system metastasis), while LDH+patients (LDH ≥460 IU/L) have increased IL-6 and IL-8 values that correlate with LDH level. Also, IL-6 correlates with C reactive protein values. Furthermore, patients with DP have significantly higher IL-6 level compared with non-DP patients. Conversely, the other analysed cytokines are similar in investigated groups of MM patients. By receiver operating characteristics curve analysis, pretherapy IL-6 level was found to be a biomarker for the occurrence of DP with cut-off value of 3.02 pg/mL. Patients in M1d stage are prevalent in the group with IL-6 ≥3.02 pg/mL that is characterised with reduced progression-free survival and higher pretherapy IL-8 and LDH.ConclusionThe evidence in this study implies that baseline IL-6 could be a biomarker of DP and poor prognosis in BRAFwt MM patients treated with pembrolizumab.

Long‐term complete remission and peripheral biomarkers in Hodgkin lymphoma patients after decitabine‐plus‐camrelizumab epi‐immunotherapy and treatment cessation

“…High serum IL‐6 level was predictive of poor efficacy and short PFS in patients with non‐small‐cell lung cancer, and decrease in IL‐6 was associated with anti‐PD‐1 responses 25,26 . Moreover, IL‐6 level was correlated to early disease progression in melanoma patients receiving anti‐PD‐1 therapy 27 . To our knowledge, the prognostic variables in cHL treated with PD‐1 blockade therapy have not been clearly examined.…”

“…25,26 Moreover, IL-6 level was correlated to early disease progression in melanoma patients receiving anti-PD-1 therapy. 27 To our knowledge, the prognostic variables in cHL treated with PD-1 blockade therapy have not been clearly examined. In this study, we reported the significance of serum baseline IL-6 for cHL patients to predict remission duration of anti-PD-1-combined immunotherapy.…”

Role of Histone Deacetylase 6 and Histone Deacetylase 6 Inhibition in Colorectal Cancer

“…Moreover, the IL-6-induced HDAC6 not only upregulated the IL-6 downstream JAK2/STAT3 pathway but also co-activated TGF-β/Smad3 signaling [ 121 ]. The increased level of circulating IL-6 has been related to metastatic disease and poor prognostic outcome in cancer patients with diverse histological tumor types, as reported in numerous studies [ 122 , 123 , 124 ].…”

Plasma D‐dimer and interleukin‐6 are associated with treatment response and progression‐free survival in advanced NSCLC patients on anti‐PD‐1 therapy

“…Since IL‐6 can be utilized as an indicator for predicting the efficacy of anti‐PD‐1 therapy, the potential correlation between these factors was further explored. The association is also between high IL‐6 with negative effects of therapy in other tumors 30 …”

“…The association is also between high IL-6 with negative effects of therapy in other tumors. 30 The associations of particular serum blood biomarkers used in routine clinical practice with treatment response and PFS of patients with advanced NSCLC on anti-PD-1 therapy were investigated, with the aim of identifying available biomarkers that could aid in predicting treatment responses or PFS with clinical applicability. Our results suggest that the D-dimer and IL-6 have significant value in predicting response to anti-PD-1 therapy.…”