Investigating the role of the complement system in immunotherapy

Aim: Cancer immunotherapy has gained importance in recent years because it is more specific and has fewer side effects than current cancer treatment methods. Strengthening the immune system against cancer cells is the main goal of cancer immunotherapy. The role of complement proteins in tumor immunology has gained importance with the application of monoclonal antibody therapy in cancer. Pembrolizumab and Nivolumab, immune checkpoint inhibitor drugs targeting programmed cell death-1, are used as second-line treatments in metastatic non-small cell lung cancer. Material and method: The aim of our study was to investigate the effects of anti-PD-1 monoclonal antibodies Nivolumab and Pembrolizumab on complement pathways in lung cancer patients. 48 s NSCLC patients who were treated in the outpatient chemotherapy unit of Inonu University Turgut Ozal Medical Center Oncology Hospital were included in the study. Clinical and demographic data of the patients were recorded. In our study, 24 patients who received Nivolumab and Pembrolizumab after chemotherapy and 24 controls who received only chemotherapy were selected. The levels of C1q, C5b and C3a complement proteins were investigated in the sera collected from the patients by ELISA method. CD59 expressions were examined in the biopsies taken from these patients in the pathology archive. Results: In the control group who received only chemotherapy, serum C5b complement protein level (105.3±38.4 ng/mL) was found to be higher than in the patient group who received monoclonal antibody (96±21.5 ng/mL). In the serum of patients who received anti-PD-1 monoclonal antibody treatment after chemotherapy, serum C1q and C3a complement protein levels (33±17 ng/mL and 552.4±380.3 pg/mL) were found to be higher than in the control group who received only chemotherapy (26.5±16.8 ng/mL and 483.9±352.6 pg/mL). Conclusion: When the effect of the combination of PD-1 targeting monoclonal antibodies and chemotherapy on complement proteins was examined in the treatment of advanced NSAIDs, a significant difference was found between the groups. In conclusion, it was shown that the combination of chemotherapy and neoadjuvant immune checkpoint inhibitors in NSAIDs caused changes in the expression level of complement proteins. Keywords: Monoclonal antiboedies, Immunotherapy, Complement system, Lung cancer.