TY - JOUR

T1 - Interleukin-1-beta concentration and neutrophil-lymphocyte ratio as possible predicting biomarkers of response to therapy with checkpoint inhibitors

AU - Орлова, Рашида Вахидовна

AU - Жукова, Наталья Владимировна

AU - Малкова, Анна Михайловна

AU - Каледина, Екатерина Александровна

AU - Губаль, Анна Романовна

AU - Шаройко, Владимир Владимирович

PY - 2021/5/20

Y1 - 2021/5/20

N2 - 3024Background: One of the discussed predictive markers of the immune therapy efficacy is the index of neutrophils to lymphocytes ratio in peripheral blood (NLr), which reflects the activity of adaptive immunity and correlates with the level of tumor-infiltrating lymphocytes (TILs). High NLr and low TILs are associated with disease progression. Interleukin-1-beta (IL-1β) is one of the main cytokines produced by the tumor microenvironment (TMO). Overexpression of the cytokine leads to a local immunosuppression. For some tumors, elevated serum IL-1β levels have been associated with a poor prognosis. The aim of this work is to analyze the serum IL-1β level as a marker of TMO activity and the NLr as a marker of adaptive immunity activity in relation to the response to therapy with checkpoint inhibitors in patients with various solid tumors. Methods: The study involved 63 patients with various solid tumors who were treated at the City Oncological Dispensary and were prescribed checkpoint inhibitors (nivolumab (n = 33), pembrolizumab (n = 23), ipilimumab + nivolumab (n = 7)). The determination of the level of IL-1β was performed using the ELISA method ("Interleukin-1-beta, ELISA-best", Novosibirsk), a clinical blood test was performed in a dispensary. The response to treatment was assessed 3-6 months after the start of therapy. Statistical analysis was carried out in GraphPad Prism. Results: Among the examined patients 49.21% (31/63) achieved partial regression or stabilization of the process (group I), and 50.79% (32/63) progressed (group II). The mean concentration of IL-1β before treatment in group I was 2.21±0.3 pg/ml, in group II - 0.98±0.2 pg/ml. NLr was increased in 7 patients from group I and in 9 patients from group II, with the mean index level being 2.9±0.39 and 3.2±0.5, respectively. There was no statistically significant difference in the concentration of IL-1β and the NLr between the studied groups. In group II, the number of patients undergoing systemic anticancer therapy before immune therapy (n = 18) was statistically significantly higher than in group I (n = 8), p = 0.033. There was no statistically significant difference in IL-1β concentration and NLr relative to previous treatment. Conclusions: Our study showed that the level of IL-1β corresponds to that of healthy donors and its isolated determination has no prognostic value. The NLr in most patients from the progression group was higher than normal, in contrast to group I, which is confirmed in the literature. The presence of previous systemic anticancer therapy was found to be associated with disease progression. The described feature can be explained by the fact that patients who received therapy before, already have a longer period of illness, a more severe clinical condition. The presence of systemic anticancer therapy does not affect the level of IL-1β and NLr.

AB - 3024Background: One of the discussed predictive markers of the immune therapy efficacy is the index of neutrophils to lymphocytes ratio in peripheral blood (NLr), which reflects the activity of adaptive immunity and correlates with the level of tumor-infiltrating lymphocytes (TILs). High NLr and low TILs are associated with disease progression. Interleukin-1-beta (IL-1β) is one of the main cytokines produced by the tumor microenvironment (TMO). Overexpression of the cytokine leads to a local immunosuppression. For some tumors, elevated serum IL-1β levels have been associated with a poor prognosis. The aim of this work is to analyze the serum IL-1β level as a marker of TMO activity and the NLr as a marker of adaptive immunity activity in relation to the response to therapy with checkpoint inhibitors in patients with various solid tumors. Methods: The study involved 63 patients with various solid tumors who were treated at the City Oncological Dispensary and were prescribed checkpoint inhibitors (nivolumab (n = 33), pembrolizumab (n = 23), ipilimumab + nivolumab (n = 7)). The determination of the level of IL-1β was performed using the ELISA method ("Interleukin-1-beta, ELISA-best", Novosibirsk), a clinical blood test was performed in a dispensary. The response to treatment was assessed 3-6 months after the start of therapy. Statistical analysis was carried out in GraphPad Prism. Results: Among the examined patients 49.21% (31/63) achieved partial regression or stabilization of the process (group I), and 50.79% (32/63) progressed (group II). The mean concentration of IL-1β before treatment in group I was 2.21±0.3 pg/ml, in group II - 0.98±0.2 pg/ml. NLr was increased in 7 patients from group I and in 9 patients from group II, with the mean index level being 2.9±0.39 and 3.2±0.5, respectively. There was no statistically significant difference in the concentration of IL-1β and the NLr between the studied groups. In group II, the number of patients undergoing systemic anticancer therapy before immune therapy (n = 18) was statistically significantly higher than in group I (n = 8), p = 0.033. There was no statistically significant difference in IL-1β concentration and NLr relative to previous treatment. Conclusions: Our study showed that the level of IL-1β corresponds to that of healthy donors and its isolated determination has no prognostic value. The NLr in most patients from the progression group was higher than normal, in contrast to group I, which is confirmed in the literature. The presence of previous systemic anticancer therapy was found to be associated with disease progression. The described feature can be explained by the fact that patients who received therapy before, already have a longer period of illness, a more severe clinical condition. The presence of systemic anticancer therapy does not affect the level of IL-1β and NLr.

UR - https://www.mendeley.com/catalogue/1c1fd0ce-fe55-3eef-9af6-14bdc0f2f4fc/

U2 - 10.1200/jco.2021.39.15_suppl.3024

DO - 10.1200/jco.2021.39.15_suppl.3024

M3 - Meeting Abstract

VL - 39

SP - 3024

EP - 3024

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 15

ER -