Clinical Research Of Cytokine-induced Killer Cells Therapy In Non-small Cell Lung Cancer Patients

Objective: To investigate the effect of CIK cells therapy on NSCLC patient’s immunity and clinical efficacy and discuss the applying of CIK cells therapy in the treatment of NSCLC patients.Methods:1 80 cases NSCLC patients were selected from Aug. 2011 to Mar. 2014 from The Fourth Hospital of Hebei Medical University. 20 cases of health individuals were as control group. According to the seventh edition IASLC, the cases of stageⅠ,Ⅱ, Ⅲ, Ⅳwas 10, 24, 28, 18, respectively. The quantities of different pathology types of tumor were 28, 50 and 2 cases as squamous carcinoma, adenocarcinoma and adenosquamous carcinoma, respectively.2 Mononuclear cells were collected from the peripheral blood of NSCLC patients, classic protocol for the ex vivo expansion of CIK cells, re-infused to the patients once a day for 3 consecutive, thirty days as one cycle. All patients accepted at least three cycles of CIK cells therapy.3 Expression of T cell subsets in peripheral blood were assessed by flow cytometry before and after CIK cells therapy respectively, and expression of T cell subsets in NSCLC patients before and after CIK cells therapy comparing with the control group were assessed.4 The effects of CIK cells therapy was assessed by the immune-related response criteria(ir RC), including immune-related complete remission(ir CR), immune-related partial remission(ir PR), immune-related stable disease(ir SD), immune-related progressive(ir PD).5 Functional status of NSCLC patients before and after CIK cells therapy was detail assessed according to Karnofsky(KFS) and ECOG criterion. General conditions of NSCLC patients before and after CIK cells therapy were observed according to quality life of cancer patients.Results: 1 The expression of T cells subsets in NSCLC patients before and after CIK cells therapy 1.1 The expression of T cells subsets in NSCLC patient’s before CIK cells therapy compared with the control groupCompared with the control group, the expression of CD3+ T cells(54.12±7.5 vs. 62.6±7.28, P<0.05), CD3+CD4+ T cells(32.95±8.12 vs. 39.21±1.73, P<0.05), CD4+/CD8+ T cells ratio(1.15±0.54 vs. 1.81±0.08, P<0.05) in the peripheral blood of NSCLC patients were significantly decreased, the expression of CD3+CD8+ T cells(32.22±8.27 vs. 24.06±0.56, P<0.05)were significantly increased. 1.2 The expression of T cells subsets in NSCLC patient’s before and after CIK cells therapyCompared with before cells therapy, the expression of CD3+ T cells(58.24±4.40 vs. 54.12±7.50, P<0.05), CD3+CD4+ T cells(41.14±7.18 vs. 32.95±8.12, P<0.05),CD4+/CD8+ T cells ratio(1.51±0.36 vs. 1.15±0.36, P<0.05) after CIK cells therapy in NSCLC patient’s were significantly improved. The expression of CD3+CD8+ T cells(26.00±6.26 vs. 32.22±8.27, P<0.05)were significantly decreased. 1.3 The expression of T cells subsets in NSCLC patient’s after CIK cells therapy compared with the control groupCompared with the control group, the expression of CD3+ T(58.24±4.40 vs. 62.60±7.28, P<0.05) and CD4+/CD8+ T cells ratio(1.51±0.36 vs. 1.81±0.08, P<0.05) in NSCLC patient’s after CIK cells therapy were significantly decreased. There was no significant difference of the expression of CD3+CD4+ T cells(41.14±7.18 vs. 39.21±1.73, P>0.05) and CD3+CD8+ T cells(26.00±6.26 vs. 24.06±0.56, P>0.05) between the control group and after CIK cells therapy. 2 Effects of CIK cells therapy on Tregs in NSCLC patient’s peripheral blood 2.1 Compared with the control group, the difference of Tregs in different stage of NSCLC patient’s before CIK cells therapyBefore CIK cells therapy, the expression of Tregs in NSCLC patients significantly increased compared with the control group(3.0±0.56 vs. 2.47±0.47, P<0.05), and the expression of NSCLC patients in stage Ⅲ~Ⅳ was significantly higher than in stage Ⅰ ~ Ⅱ(3.50±0.97 vs. 3.0±0.56, P<0.05). 2.2 Compared with before CIK cells therapy, the expression of Tregs in different stage of NSCLC patient’s after CIK cells therapy.Compared with before CIK cell therapy, the expression of Tregs in stageⅠ~Ⅱ(2.53±0.54 vs. 3.0±0.56, P<0.05)and in stage Ⅲ~Ⅳ(2.87±0.62 vs. 3.5±0.97, P<0.05)were significantly decreased in NSCLC patients after CIK cells therapy. 2.3 Compared with the control group, the expression of Tregs in different stage of NSCLC patient’s after CIK cells therapyAfter CIK cells therapy, the expression of Tregs in stage Ⅰ ~ Ⅱ(2.53±0.54 vs. 2.47±0.47, P<0.05) were significantly decreased compared with the control group. There was no significantly difference of the expression of Tregs between stage Ⅲ~Ⅳ and the control group(2.87±0.62 vs. 2.47±0.47, P>0.05). 2.4 The expression difference of Tregs in different stage of NSCLC patient’s after CIK cells therapyAfter CIK cells therapy, the expression of Tregs in stage Ⅰ~Ⅱcompared with in stage Ⅲ~Ⅳ(2.53±0.54 vs. 2.87±0.62, P<0.05)were significantly decreased. 3 The effect of CIK cells therapy on clinical efficacy of NSCLC patientsCompared with before CIK cells therapy, there was no significant difference of the expression of overall response rate(ORR, P>0.05), while disease effective rate was significantly increased(P<0.05) in NSCLC patients according to the ir RC criteria. 4 The changes of patient’s general conditions in NSCLC patientsAfter CIK cells therapy, there was no significant difference of functional status of patient after CIK cells therapy in NSCLC patients(P>0.05). Also, there was no significant difference of functional status of patient’s general conditions such as insomnia, pain(P>0.05). Howere, there was significant difference of loss of appetite, physical decline in NSCLC patients(P<0.05).Conclusions:1 CIK cells therapy could enhance NSCLC patient’s immune killer function, improve body’s antitumor immune function by regulate the proportion of T lymphocytes subsets of the peripheral blood in NSCLC patients. The immunosuppressive status in advanced stage of NSCLC patients was seriously than early stage.2 CIK cells therapy could reverse body’s immunosuppressive state in a certain condition and reduce the immune escape.3 The curative effect of tumor therapy was improved by re-infused CIK cells. CIK cells therapy could also improve patient’s general conditions and quality of life.