Spectrum of adipokines, batokines, myokines, and growth factors in blood serum of patients with various stages of lung cancer and with immunotherapy with PD-1/PD-L1 inhibitors.

Abstract

e21069 Background: Metabolites of the intestinal microbiota, including adipokines, batokins, and myokines, are involved in carcinogenesis, antitumor immune defense and ensuring the effectiveness of antitumor treatment, including chemotherapy and immunotherapy. Methods: The study included 100 patients with lung cancer (LC), 70% males and 30% females: stage I – 10%, II - 14%, III – 50%, IV – 26%. 21 patients (12 males and 9 females) received treatment with PD-1/PD-L1 inhibitors: stage I - 2 (9%), II - 1 (5%), III - 5 (24%), IV - 12 (62%). Therapy included atezolizumab and pembrolizumab – 9 patients each (43%), nivolumab – 3 (14%). Complete response was registered in 2 (9%), partial response in 5 (24%), stabilization - 4 (19%), progression - 8 (38%). One patient developed an immune-mediated adverse event (Guillain-Barré syndrome), so checkpoint inhibitors (CPI) were canceled. Serum levels of adipokines, myokines, batokines, and growth factors were determined by ELISA before and during treatment. The control group included 100 healthy donors. Results: Levels of VEGF and NGF were statistically significantly higher in patients with lung cancer than in donors, without differences in other parameters. Differences were revealed depending on the LC stage: leptin was higher in stages I and IV (Me 52.8 and 46.3 ng/ml, respectively) compared with stages II and III (Me 27.4 and 16.4 ng/ml, respectively) and with donors (Me 12.5 ng/ml). In stages III and IV, levels of VEGF increased (Me 504 and 473 pg/ml, respectively; in donors Me 239 pg/ml), while BDNF decreased (Me 2.7 and 0.4, respectively, in donors Me 12.6 μg/ml); NGF in stages I and II was not detected, unlike stages III and IV. Immunotherapy with CPI elevated levels of adiponectin (Me 12.5 and 16 μg/ml, respectively), and reduced levels of myostatin (Me 26.4 and 2.8 μg/ml, respectively) and NGF (Me 130 and 53 pg/ml, respectively). Only NGF could be regarded as a predictive factor of the response to CPI, since it was detected in high amounts only in patients with subsequent LC progression, while in patients with a positive response to treatment or stabilization, it was absent both before and after immunotherapy. Conclusions: Serum levels of some adipokines, myokines, batokins, and growth factors in LC patients differ depending on the cancer stage and the result of CPI immunotherapy; thus, NGF can be used as a predictor of the immunotherapy effectiveness. The study was performed with financial support from the Federal Medical and Biological Agency of Russia under contract No. 0373100122120000017 dated 20.05.2020.