Characteristics Of CD8~+CD56~+NKT Cells In Patients With Non-small Cell Lung Cancer

Background:Non-small cell lung cancer(NSCLC)is a main histologic type of lung cancer which ranks the first in cancer morbidity and mortality in the world.Natural killer T(NKT)cells are the bridge between innate and adaptive immunity,widely involved in the immune response in vivo.In vitro experiments showed that CD8~+CD56~+NKT subsets had strong cytotoxicity,and a large amount of granulocase B and perforin could be rapidly released after tumor antigen stimulation.However,the progression of malignant tumor disease is often accompanied by immunosuppression,and the changes in the number and status of CD8+CD56+NKT cells in tumor microenvironment have not been determined.Objective:Detecting and comparing the frequency of CD8~+CD56~+NKT cells and their expression rate of CD57、Ki67、NKG2D、CD69 in peripheral blood from healthy individuals and the NSCLC patients.Aim to investigate the status of such NKT cell subsets in NSCLC patients,in further to understand the role of such cells in tumor immunity,so as to provide a basis for using such cells for cellular immunotherapy.Methods:47 healthy subjects were recruited as controls,and 47 NSCLC patients were recruited as lung cancer group.First,clinical data as well as routine laboratory examination data in two groups were collected and analyzed.Secondly,the frequency of CD8~+CD56~+NKT cells and their expression rate of CD57,Ki67,NKG2D and CD69 in two groups were analyzed by four-color flow cytometry.Finally,analyzing the possible influencing factors of CD8~+CD56~+NKT cells.Results:(1)The number of lymphocytes,erythrocytes,and the level of hemoglobin,total protein and albumin of NSCLC group were lower than control(P<0.05),while the level of alanine aminotransferase,carcinoembryonic antigen of NSCLC group were higher than control(P<0.05).(2)The frequency of CD8~+CD56~+NKT cells in peripheral blood of NSCLC group was significantly lower than control(P<0.05).The expressing rate of CD57 and NKG2D on NKT cells were significantly reduced(P<0.05),in contrast,the expression rate of CD69 was significantly higher than control(P<0.05),while the difference in Ki67 of two groups was not statistically significant(P>0.05).(3)Different gender,age(≤60 years old,>60 years old),pathological type(squamous cell carcinoma,adenocarcinoma),TNM stages(stageⅠ~Ⅱ、stageⅢ、stageⅣ)and treatment schemes(first visit,chemotherapy,targeted therapy,and chemotherapy combined with targeted therapy)did not affect the frequency of CD8~+CD56~+NKT cells NSCLC patients,the difference was not statistically significant(P>0.05).Conclusion:(1)Lung cancer patients need to be cautious of malnutrition,anemia and hepatic dysfunction.(2)The percentage of peripheral blood CD8~+CD56~+NKT cells in NSCLC patients was decreased,while the proportion of the activated cells was increased,with weakened toxicity and exhaustion.It was speculated that the frequency and status ofCD8~+CD56~+NKT cells were dynamically changed during tumor progression,that is,theyparticipated in the anti-tumor immune response in the early stage of NSCLC,and they were largely consumed by the long-term tumor antigen stimulation,and were exhausted in the late stage of tumor.Although they could receive the stimulation of activation signal,their cytotoxic effect was weakened.(3)The frequency of CD8~+CD56~+NKT cell in lung cancer group was not affected by gender,age,pathological type TNM stages and treatment schemes.