Relationship between IL-1β and IL-8 serum concentrations in patients with metastatic melanoma taking checkpoint inhibitors.

Authors

Rashida Orlova

Rashida Orlova

Saint-Petersburg State University, Saint-Petersburg, Russian Federation

Rashida Orlova , Anna Malkova , Natalia V. Zhukova , Ekaterina Kaledina , Alexandra Demchenkova , Polina Naymushina , Vladimir Sharoyko

Organizations

Saint-Petersburg State University, Saint-Petersburg, Russian Federation, Saint-Petersburg State University, Medical Faculty, Saint-Petersburg, Russian Federation, SPb SBIH City Clinical Oncology Dispensary, Saint-Petersburg, Russian Federation, Saint-Petersburg State University, Saint Petersburg, Russian Federation, Saint-Petersburg State University, St. Petersburg, Russian Federation

Research Funding

Other

Background: Melanoma is a disease that is most often treated with immune checkpoint inhibitors (ICI). The principle mechanism of ICI is based on the activation of the antitumor immune response. This therapy is not effective in all patients, which may be due to the immunosuppressive effect of tumor microenvironment (TME). IL-1β is one of the most important participants in the TME, however, it is difficult to determine it in blood serum, in contrast to IL-8, the synthesis of which is induced by IL-1β. The study aims to determine the relationship between IL-1β and IL-8 in patients with metastatic (mts) melanoma and to reveal their diagnostic significance. Methods: The study involved 28 patients (pts) with mts melanoma taking ICI. The level of IL-1β and IL-8 in blood serum was determined using the ELISA method. Statistical analysis was performed in GraphPad Prism 6 (Graph Pad Software, USA) using Fisher, Mann-Whitney, ROC, Wilcoxon matched-pairs signed rank test, Spearman statistical analysis. Results: IL-1β was detected in 35.5% (11/31) of patients before therapy, while an elevated level was recorded in only one patient. IL-8 was found in all patients, an elevated level before therapy was observed in 64.5% (20/31) of cases, after 2-3 months - in 35.5% (11/31). During ICI therapy, a statistically significant decrease in the concentration of IL-1β (p = 0.0498) and IL-8 (p = 0.0002) were observed. In the presence of IL-1β, the level of IL-8 was statistically higher (139.6±65.26 pg/ml), p = 0.024, while a mean positive correlation was found between IL-1β and IL-8 concentrations (R = 0.6469, p = 0.035). According to ROC analysis (Area = 0.76), with an increase in the concentration of IL-8 more than 42.31 pg/ml with a diagnostic sensitivity of 66.67% and a specificity of 90.00%, it can be assumed that the level of IL-1β will be detected in the patient (p = 0.025). Conclusions: According to the study, with an IL-8 concentration of more than 42.31 pg/ml in patients with mts melanoma, the presence of IL-1β in the blood serum can be expected. At the same time, the level of IL-8 correlated with the level of IL-1β. It can be assumed that high level of IL-8 may indicate the overexpression IL-1β in TME and it`s high activity, which may be associated with the possible risk of low ICI efficacy.

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Abstract Details

Meeting

2022 ASCO Annual Meeting

Session Type

Publication Only

Session Title

Melanoma/Skin Cancers

Track

Melanoma/Skin Cancers

Sub Track

Advanced/Metastatic Disease

Citation

J Clin Oncol 40, 2022 (suppl 16; abstr e21510)

DOI

10.1200/JCO.2022.40.16_suppl.e21510

Abstract #

e21510

Abstract Disclosures