Clinical Study Of NK Cells In The Treatment Of Advanced Hepatocellular Carcinoma

Background and objective: Primary hepatic carcinom is one of the most severe malignancy in digestive system.Its incidence is increased gradually with the elevated prevalence of chronic hepatitis,cirrhosis and obesity.Nowadays,surgery has been preferred for the treatment of primary liver cancer,but only 15% show indications of surgery.Moreover,part of the patients showed a 5-year survival of merely 21% after surgery.Hepatic transplantation is considered as an effective method for the local management of the disease,however,an incidence of recurrence of 15% is reported.With the advance of medical technique,diverse methods have been developed for the local management of the primary liver cancer,which contribute to the increased response rates of these patients.However,the treatment of such disease is still a challenge and the mortality rate is still high.Therefore,it is urgent to find effective strategies for the treatment of hepatic cancer,especially the aged patients with poor response and decreased life quality.Cellular immunotherapy,featured by high safety,excellent anti-cancer property,and complete elimination of small and residue cancer lesions effectively,has been considered as a new alternation for the surgery,chemotherapy and radiotherapy.Such therapy could enhance the immune function to kill cancer cells and control the growth of the cells without killing the normal cells.Besides,it could attenuate the immunosuppressive function induced by chemotherapy and radiotherapy,and increase the sensitivity and treatment outcome of these regimens.Thus,it has been considered as an important method as it is complementary to the conventional methods.Accordingly,it contributes to the elevation of immune function and life quality,which brings new hope for the patients.Natural killer(NK)cells,as an important part of the immune system,are effective to eliminate the cancer,virus,parasitic bacterium,as well as aging and differentiated cells.These cells could recognize the malignant cancer cells directly,and are activated by the assistance of helper cells to kill the cancer cells.Meanwhile,NK cells could elevate the immune function,which is considered as an important effector cell for the immunotherapy of cancer.Nowadays,these cells are extensive applied in clinical practice due to the specific cancer killing effects.In this study,we aim to investigate the short-term clinical efficiency,safety,immune function and cell viability in advanced hepatic cancer patients received NK cell therapy.Our study contributed to the standardization of the system,time point and regimen of cellular immunotherapy,and establishing of efficiency evaluation criteria.Meanwhile,it may improve the clinical efficiency,and provide solid evidence for the standardized and individualized treatment modality for the advanced malignant tumor.Methods: Fifty-four advanced hepatic cancer patients received standard treatmentin our hospital were included in this study.The peripheral blood was collected from each patient or donor.NK cells were generated after in vitro culture and induction.Cell transfusion was performed on day 14 and 15 after proliferation in vitro.The short-term clinical efficiency,safety and KPS score were evaluated.Moreover,flow cytometry was performed to determine the number of 10 lymphocytes and NK viability before and 1month after cellular therapy.On this basis,a comparison was performed to the number of lymphocyte subsets and viability of NK cells before and after treatment.Meanwhile,the association between these parameters and clinical efficiency was evaluated.Results: Fifty-four advanced hepatic cancer patients received NK cell therapy were included in this study.The improvement,quality of life,total effective rate,response rate,as well as effects of disease-control rate on the efficiency were evaluated comprehensively.Besides,a dynamic observation on the lymphocyte subsets,the changes of NK viability before and after treatment,as well as its correlation between the efficiency was carried out.1.Among the 54 patients,a total beneficial rate of 68% was obtained in the KPS score after NK cell immunotherapy.Nine patients showed partial response.Thirty-one patients showed stable disease,and fourteen patients showed progressive disease(PD).The total partial response rate is 16.6%,the total disease-control rate was 74.1%.No statistical difference was identified in the lymphocyte subsets before and after treatment(P>0.05).The NK viability showed remarkable elevation after treatment compared with the baseline levels [(5.06±4.39)%,vs(7.36±4.31)%,P<0.05].2.For the safety of NK cell immunotherapy,except one patient get fever,no patients showed adverse events such as rash,vomiting or diarrhea.Conclusions:1.NK cell immunotherapy contributed to the improvement of the quality of life and extension of survival.Besides,it could modulate the immune function,and promote the clinical efficiency.Moreover,such therapy attenuated the disease progression of advanced hepatic cancer,and extended the survival time.It could be served as an effective adjunctive therapy to the conventional treatment regimens including surgery,chemotherapy and radiotherapy.2.No statistical difference was identified in the lymphocyte subsets before and after NK cell immunotherapy.3.The NK viability showed remarkable elevation after treatment compared with the baseline levels in part of the patients(P<0.05).Such therapy could modulate the immune function effectively.