The influence of autologous cytokine-induced killer cell treatment on the objective efficacy and safety of gefitinib in advanced non-small cell lung cancer

Objective The aim of the study was to observe the influence of autologous cytokine-induced killer cell （CIK） treatment on the objective efficacy and safety of gefitinib in advanced non-small ceil lung cancer （NSCLC）. Methods Sixty-six patients with NSCLC received gefitinib as second-line treatment. They were randomly divided into 2 groups, and informed consent forms were signed before grouping. Gefitinib was administrated to the control group, and autologous CIK treatment was added to the observation group. The objective treatment and adverse reactions were evaluated in both groups. Results The objective response rate （ORR） and the disease control rate （DCR） of the observation group were slightly higher than those of the control group, although no statistical differences were found between the 2 groups （P 〉 0.05）. The incidences of diarrhea, fatigue, anorexia, oral ulcers, and myelosuppression in the observation group were much lower than those in the control group （P 〈 0.05）. However, there were no statistical differences between the incidences of skin rash, and liver and kidney toxicities （P 〉 0.05）. Conclusion Autologous CIK in combination with gefitinib is effective as second-line treatment fore ad- vanced NSCLC, and can significantly reduce adverse reactions and improve the objective efficacy.

Cisplatin pretreatment enhances anti-tumor activity of cytokine-induced killer cells

AIM： To investigate whether cisplatin （DDP） enhances the anti-tumor activity of cytokine- induced killer （CIK） cells in a murine colon adenocarcinoma model. METHODS： Tumor size and weight served as indicators of therapeutic response. Immunohistochemistry was performed to observe intratumoral lymphocyte infiltration and tumor microvessel density. Changes in the percentage of regulatory T （Treg） cells within the spleens of tumor-bearing mice preconditioned with DDP were monitored using flow cytometry. RESULTS： A marked T cell-dependent, synergistic anti- tumor effect of the combined therapy was observed （1968 ± 491 mm3 ys 3872 ＋ 216 mm3; P = 0,003）, Preconditioning chemotherapy with DDP augmented the infiltration of CD3＋ T lymphocytes into the tumor mass and reduced the percentage of both intratumoral and splenic Treg cells. CONCLUSION： Preconditioning with DDP markedly enhances the efficacy of adoptively transferred CIK cells, providing a potential clinical modality for the treatment of patients with colorectal cancer.

Adjuvant treatment for triple-negative breast cancer: a retrospective study of immunotherapy with autologous cytokine-induced killer cells in 294 patients

Objective: To examine the efficacy and safety of a sequential combination of chemotherapy and autologous cytokine-induced killer(CIK) cell treatment in triple-negative breast cancer(TNBC) patients.Methods: A total of 294 post-surgery TNBC patients participated in the research from January 1, 2009 to January 1, 2015. After adjuvant chemotherapy, autologous CIK cells were introduced in 147 cases(CIK group), while adjuvant chemotherapy alone was used to treat the remaining 147 cases(control group). The major endpoints of the investigation were the disease-free survival(DFS) and overall survival(OS). Additionally, the side effects of the treatment were evaluated.Results: In the CIK group, the DFS and OS intervals of the patients were significantly longer than those of the control group(DFS:P = 0.047;OS: P = 0.007). The multivariate analysis demonstrated that the TNM(tumor-node-metastasis) stage and adjuvant CIK treatment were independent prognostic factors for both DFS [hazard ratio(HR)= 0.520, 95% confidence interval(CI):0.271-0.998, P = 0.049;HR = 1.449, 95% CI:1.118-1.877, P = 0.005, respectively] and OS(HR=0.414, 95% CI:0.190-0.903, P = 0.027;HR= 1.581, 95% CI:1.204-2.077, P = 0.001, respectively) in patients with TNBC. Additionally, longer DFS and OS intervals were associated with increased number of CIK treatment cycles(DFS: P = 0.020;OS: P = 0.040). The majority of the patients who benefitted from CIK cell therapy were relatively early-stage TNBC patients.Conclusion: Chemotherapy in combination with adjuvant CIK could be used to lower the relapse and metastasis rate, thus effectively extending the survival time of TNBC patients, especially those at early stages.

Intraperitoneal perfusion of cytokine-induced killer cells with local hyperthermia for advanced hepatocellular carcinoma

AIM:To study the effect and tolerance of intraperitoneal perfusion of cytokine-induced killer(CIK) cells in combination with local radio frequency(RF) hyperthermia in patients with advanced primary hepatocellular carcinoma(HCC).METHODS:Patients with advanced primary HCC were included in this study.CIK cells were perfused intraperitoneal twice a week,using 3.2 × 10 9 to 3.6 × 10 9 cells each session.Local RF hyperthermia was performed 2 h after intraperitoneal perfusion.Following an interval of one month,the next course of treatment was administered.Patients received treatment until disease progression.Tumor size,immune indices(CD3 +,CD4 +,CD3 + CD8 +,CD3 + CD56 +),alpha-fetoprotein(AFP) level,abdominal circumference and adverse events were recorded.Time to progression and overall survival(OS) were calculated.RESULTS:From June 2010 to July 2011,31 patients diagnosed with advanced primary HCC received intraperitoneal perfusion of CIK cells in combination with local RF hyperthermia in our study.Patients received an average of 4.2 ± 0.6 treatment courses(range,1-8 courses).Patients were followed up for 8.3 ± 0.7 mo(range,2-12 mo).Following combination treatment,CD4 +,CD3 + CD8 + and CD3 + CD56 + cells increased from 35.78% ± 3.51%,24.61% ± 4.19% and 5.94% ± 0.87% to 45.83% ± 2.48%(P = 0.016),39.67% ± 3.38%(P = 0.008) and 10.72% ± 0.67%(P = 0.001),respectively.AFP decreased from 167.67 ± 22.44 to 99.89 ± 22.05 ng/mL(P = 0.001) and abdominal circumference decreased from 97.50 ± 3.45 cm to 87.17 ± 4.40 cm(P = 0.002).The disease control rate was 67.7%.The most common adverse events were low fever and slight abdominal erubescence,which resolved without treatment.The median time to progression was 6.1 mo.The 3-,6-and 9-mo and 1-year survival rates were 93.5%,77.4%,41.9% and 17.4%,respectively.The median OS was 8.5 mo.CONCLUSION:Intraperitoneal perfusion of CIK cells in combination with local RF hyperthermia is safe,can efficiently improve immunological status,and may prolong survival in HCC patients.

Immunotherapy with dendritic cells and cytokine-induced killer cells for hepatocellular carcinoma: A meta-analysis

BACKGROUND Hepatocellular carcinoma(HCC) has been revealed as the second most common cause of cancer-related deaths worldwide. The introduction of cell-based immunotherapy, including dendritic cells(DCs) and cytokine-induced killer cells(CIKs), has brought HCC patients an effective benefit. However, the efficacy and necessity of cellular immunotherapy after different interventional therapy remains to be further explored.AIM To investigate the efficacy of cellular immunotherapy, involving DCs and CIKs,combined with different conventional treatments of HCC.METHODS We performed a literature search on PubMed and Web of Science up to February15, 2019. Long-term efficacy(overall survival and recurrence) and short-term adverse effects were investigated to assess the effectiveness of immunotherapy with DCs and/or CIKs. Review Manager 5.3 was used to perform the analysis.RESULTS A total of 22 studies involving 3756 patients selected by eligibility inclusion criteria were forwarded for meta-analysis. Combined with the conventional clinical treatment, immunotherapy with DCs and/or CIKs was demonstrated to significantly improve overall survival at 6 mo [risk ratio(RR) = 1.07;95%confidence interval(CI): 1.01-1.13, P = 0.02], 1 year(RR = 1.12;95%CI: 1.07-1.17, P< 0.00001), 3 years(RR = 1.23;95%CI: 1.15-1.31, P < 0.00001) and 5 years(RR =1.26;95%CI: 1.15-1.37, P < 0.00001). Recurrence rate was significantly reduced by cellular immunotherapy at 6 mo(RR = 0.50;95%CI: 0.36-0.69, P < 0.0001) and 1 year(RR = 0.82;95%CI: 0.75-0.89, P < 0.00001). Adverse effect assessment addressed that immunotherapy with DCs and/or CIKs was accepted as a safe,feasible treatment.CONCLUSION Combination immunotherapy with DCs, CIKs and DC/CIK with various routine treatments for HCC was evidently suggested to improve patients’ prognosis by increasing overall survival and reducing cancer recurrence.

Hepatocellular carcinoma-specific immunotherapy with synthesized α1,3-galactosyl epitope-ulsed dendritic cells and cytokine-induced killer cells

AIM： To evaluate the safety and clinical efficacy of a new immunotherapy using both α-Gal epitope-pulsed dendritic cells （DCs） and cytokine-induced killer cells. METHODS： Freshly collected hepatocellular carcinoma （HCC） tumor tissues were incubated with a mixture of neuraminidase and recombinant αl,3-galactosyltrans- ferase （αI,3GT） to synthesize α-Gal epitopes on car- bohydrate chains of the glycoproteins of tumor mem- branes. The subsequent incubation of the processed membranes in the presence of human natural anti-Gal IgG resulted in the effective phagocytosis to the tumor membrane by DCs. Eighteen patients aged 38-78 years with stage 111 primary HCC were randomly chosen for the study; 9 patients served as controls, and 9 patients were enrolled in the study group.RESULTS： The evaluation demonstrated that the pro- cedure was safe; no serious side effects or autoimmune diseases were observed. The therapy significantly pro- longed the survival of treated patients as compared with the controls （17.1 ± 2.01 mo vs 10.1 ±4.5 mo, P = 0.00121）. After treatment, all patients in the study group had positive delayed hypersensitivity and robust systemic cytotoxicity in response to tumor lysate as measured by interferon-y-expression in peripheral blood mononuclear cells using enzyme-linked immunosorbent spot assay. They also displayed increased numbers of CD8-, CD45RO- and CD56-positive cells in the peripheral blood and decreased α-fetoprotein level in the se- rum. CONCLUSION： This new tumor-specific immunotherapy is safe, effective and has a great potential for the treat- ment of tumors.

Effect of dendritic cell/cytokine-induced killer cell immunobiological cancer therapy combined with adjuvant chemotherapy in patients with triple-negative breast cancer

Objective The aim of the present study was to investigate the effect of dendritic cell(DC)/cytokine-induced killer cell(CIK) immunobiological cancer therapy in patients with triple-negative breast cancer(TNBC) who underwent adjuvant chemotherapy. Methods From January 2010 to October 2013, 120 patients with postoperative TNBC were recruited and included in the study. Patients were enrolled in one of two groups according to whether they accepted DC/CIK immunobiological cancer therapy during adjuvant chemotherapy; the patients in the DC/CIK group underwent adjuvant chemotherapy combined with DC/CIK immunobiological cancer therapy, and the control group underwent adjuvant chemotherapy alone. When six cycles of adjuvant chemotherapy and six cycles of DC/CIK immunobiological cancer therapy had been completed, differences between the two groups with regard to quality of life(Qo L), immunological indicators(CD3, CD4, CD8, and NK cell levels), disease-free survival(DFS), and side effects of chemotherapy and DC/CIK treatment were evaluated.Results In the DC/CIK group, the proportion of NK cells and CD3+ and CD4+ T-cell subgroups significantly increased, and the proportion of CD8+ cells decreased when they were compared before and after DC/CIK therapy(P < 0.05). However, there were no significant changes in the control group. By the final follow-up, DFS of the treatment group and the control group was 38.4 and 34.2 months, respectively. The Qo L improved in the patients treated with chemotherapy plus DC/CIK therapy compared with the patients treated with chemotherapy alone, and the difference between groups was significant(P < 0.05). The side effects of two groups were tolerable and not significantly different between the two groups.Conclusion The DC/CIK treatment had potential benefits for patients with TNBC compared with the control group, and was not associated with any obvious side effects. Therefore, DC/CIK therapy is a safe and effective method for the treatment of TNBC.

Preliminary Study of Local Immunotherapy with Autologous Cytokine-Induced Killer Cells for Glioma Patients

OBJECTIVE Cytokine-induced killer （CIK） cells are T-cells that display effective anti-tumor activity. In this stud, we investigated the anti-tumor activity of CIK cells in vitro, and conducted a preliminary investigation using autologous CIK cells to treat glioma patients through local administration. METHODS The CIK cells were derived from peripheral blood monocytes （PBMCs） of the glioma patients. The anti-tumor activity of the CIK cells against human T98-G glioma cell was tested in vitro. In addition, the autologous CIK cells were locally administrated into the tumor cavity in the malignant glioma patients through an Ommaya reservoir which was pre-inserted during tumor resection. The 4 x 108 CIK cells in a 5 ml suspension were injected once a week 2 times per cycle. Five hundreds KU of IL-2 was injected every other day. RESULTS （i） With incubation, the CIK cells showed dual staining of CD3^＋CD56^＋ with a positive rate of 3.45% on day 10 and 55.2% on day 30. In vitro anti-tumor activity （against T98-G cells） of the CIK cells reached the highest level after 18 days of incubation with different effector/target （E：T） ratios. （ii） Six patients received autologous CIK cell treatment （10 cycles）. Two patients showed no recurrence and are still alive （24 and 10 months）, while 4 cases had a recurrence 3 of which have died. The mean survival time from the first CIK cell treatment to the end of follow-up was 12.5 months. The main side-effects of the local CIK cell treatment was brain edema, which was controlled by mannitol in most of the cases. However for one patient injection of CIK cells and IL-2 had to be discontinued. CONCLUSION In vitro CIK cells are effective anti-glioma T-cells. Local therapy with CIK cells has potential anti-glioma efficacy and tolerable side-effects.

In vitro incubation of cytokine-induced killer cells from patients with and without hepatitis B virus and a cell subset analysis

Objective The aim of the study was to explore the difference between immune cell subsets during the incubation of cytokine-induced kill cells （CIKs） from patients with and without hepatitis B virus （HBV）. Methods Peripheral blood samples were extracted from 50 tumor patients, and were divided into two groups according to the presence or absence of HBV. The proliferation rate and activity of CIK cells were examined based on counts on days 1, 5, 7, 9, 11, 13, and 15 of culture. Additionally, the CD3＋, CD4＋, CD8＋, CD3＋CD8＋, C＋）3＋CD4＋, and CD3＋CD56＋ T cell populations were analyzed by flow cytometry on days 5, 7, 10, 13, and 15 of culture. Results Proliferation over a 15-day period was higher in the HBV-positive group than in the negative group （280-fold vs. 180-fold increase, respectively）, but there was no significant difference between the two groups at each time point. The frequencies of CD3＋, CD8＋ T, CD3＋CD8＋, and CD3＋CD56＋T cells increased over time, while those of CD4＋ and CD3＋CD4＋ T cells decreased over time, and these changes were greater in the positive group than in the negative group. The differences in CD8＋ T cells and CD3＋CD4＋ T cells between the two groups were significant （P 〈 0.05）. Conclusion The proliferative capacity of CIK cells was higher for patients in the HBV-positive group than those in the HBV-negative group, and immune cell subsets were more favorable in the HBV-positive group than the neaative arouD.

Natural killer cells in hepatitis C:Current progress

Patients infected with the hepatitis C virus(HCV) are characterized by a high incidence of chronic infection, which results in chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. The functional impairment of HCV-specific T cells is associated with the evolution of an acute infection to chronic hepatitis. While T cells are the important effector cells in adaptive immunity, natural killer(NK) cells are the critical effector cells in innate immunity to virus infections. The findings of recent studies on NK cells in hepatitis C suggest that NK cell responses are indeed important in each phase of HCV infection. In the early phase, NK cells are involved in protective immunity to HCV. The immune evasion strategies used by HCV may target NK cells and might contribute to the progression to chronic hepatitis C. NK cells may control HCV replication and modulate hepatic fibrosis in the chronic phase. Further investigations are, however, needed, because a considerable number of studies observed functional impairment of NK cells in chronic HCV infection. Interestingly, the enhanced NK cell responses during interferon-α-based therapy of chronic hepatitis C indicate successful treatment. In spite of the advances in research on NK cells in hepatitis C, establishment of more physiological HCV infection model systems is needed to settle unsolved controversies over the role and functional status of NK cells in HCV infection.

Side Effects during Treatment of Advanced Gastric Carcinoma by Chemotherapy Combined with CIK-cell Transfusion in Elderly People

OBJECTIVE To study the side effects and therapeutic results of autologous cytokine-induced killer （CIK） cell treatment in elderly patients with advanced gastric cancer. METHODS CIK cells were induced and cultured using biotechnics in vitro, and then the cells were infused back into the patients. Sixty elderly gastric cancer patients treated by chemotherapy （FOLFOX4 protocol） were followed-up. Among them, 29 patients were treated with CIK cells during application of chemotherapy. Short-term curative effects and adverse events from the CIK transfusion and chemotherapy were observed. RESULTS Eight cases developed partial remission （PR）, 9 cases moderate remission （MR）, 7 cases stable disease （SD） and 5 cases progressive disease （PD）. Out of a total of 29 patients who received chemotherapy combined with autologous CIK therapy, the total remission rate （PR ＋ MR） was 58.6%. The total remission rate following chemotherapy alone was 45.2%, including 5 PR cases, 9 MR cases, 7 SD cases, and 10 PD cases. There was a relatively lower rate of severe chemotherapic toxicities in the CIK-cell transfusion group. Side effects of autologous CIK transfusion included chills （13 cases）, fever （9 cases）, nausea and vomiting （1 case） and general malaise （3 cases）. Side effects were treated with conventional therapy resulting in their amelioration. No patients developed shock, blood capillary leakage syndrome, or abnormalities in routine blood, urine, liver and renal function tests.CONCLUSION Adoptive immunotherapy with autologous CIK cells may decrease the clinical signs and symptoms of elderly patients who suffer from advanced gastric cancer. Adverse reactions of patients can be alleviated by conventional therapy. Autologous CIK-cell transfusion may improve endurance to chemotherapy.

The clinical effects of DC-CIK cells combined with chemotherapy in the treatment of advanced NSCLC

Objective: The aim of the study was to evaluate the safety and therapeutic effects of autologous dendritic cells co-cultured with cytokine-induced killer cells (DC-CIK) combined with chemotherapy in advanced non-small cell lung cancer (NSCLC) patients. Methods: Fifty patients with advanced NSCLC (stages III to IV), who had received therapies in our Center (Department of Biotherapy, Affiliated to Cancer Hospital of Shanxi Medical University, Taiyuan, China) from August 2008 to January 2010, were treated by DC-CIK + chemotherapy as the combined treatment group; fifty advanced NSCLC patients treated with chemotherapy at the same time served as controls. The immunologic function, short-term therapeutic effects, the 1-year survival rate, the life quality, the chemotherapy side effects were compared between the two groups, the safety and therapeutic effects of DC-CIK cells therapy were observed too. Results: There was no obvious change of subsets of T cells in peripheral blood before and after therapy in DC-CIK + chemotherapy group, and IFN-γ was improved after therapy in this group (P < 0.05); in chemotherapy alone group, the ratios of CD3+CD4+, CD3+CD8+, CD3-CD56+ cells and the secretion of IL-2, TNF-α decreased significantly after therapy (P < 0.05); the ratios of CD3+CD8+, CD3+CD56+ were improved after cell culture (P < 0.05). The disease control rate (DCR) of DC-CIK + chemotherapy group was higher than that in the chemotherapy alone group (78.0% vs 56.0%, P < 0.05); the 1-year survival rates of DC-CIK + chemotherapy group and chemotherapy alone group were 50% and 44% respectively, had no significant difference. Compared with chemotherapy alone group, the occurrence of chemotherapy side effects (including bone marrow suppression, nausea and vomiting, peripheral nerve toxicity) was less in the DC-CIK + chemotherapy group (P < 0.05). The physical and appetite were better in DC-CIK + chemotherapy group after therapy. Conclusion: To compare with simple chemotherapy, DC-CIK + chemotherapy for advanced NSCLC is safe and effective, and it can improve patients' life quality and remission rate, and prolong their survival time.

The effects of CIK cells on the treatment of renal cell carcinoma

Objective： To observe the effects of cytokine-induced killer （CIK） cells on the treatment of renal cell carcinoma. Methods： Twenty-eight postoperative cases with stage Ⅰ or stage Ⅱrenal cell carcinoma were admitted in our hospital from January 2002 to June 2006, all cases were pathologically confirmed, and were divided into group A （18 cases） and group B （10 cases）. Group A was administrated 3-12 periods of CIK cells treatment combined with 5-7 cycles of IL-2 and INFα-2b, together with 4 cycles of chemotherapy （5-Fu ＋ CF）. Group B was given 4 cycles of chemotherapy （5-Fu ＋ CF） and 5-7 cycles of IL-2 and INFa-2b. Results： Three cases in group A had metastatic masses in two lungs within 1 year and died within 2 years postoperatively. The other 15 cases are still alive and in good health. Six cases in group B had metastatic masses in two lungs or/and in abdominal cavity within 1 year, and 4 of them died within 2 years. All the 6 cases died within 3 years. The other 4 cases are still alive and in good health. Conclusion： CIK cells are safe and effective for the treatment of stage I or stage II renal cell carcinoma, which should be further widely used.

Aggressive natural killer cell leukemia with skin manifestation associated with hemophagocytic lymphohistiocytosis:A case report

BACKGROUND Aggressive natural killer cell leukemia(ANKL)is a rare natural killer cell neoplasm characterized by systemic infiltration of Epstein–Barr virus and rapidly progressive clinical course.ANKL can be accompanied with hemophagocytic lymphohistiocytosis(HLH).Here,we report a case of ANKL with rare skin lesions as an earlier manifestation,accompanied with HLH,and review the literature in terms of etiology,clinical manifestation,diagnosis and treatment.CASE SUMMARY A 30-year-old woman from Northwest China presented with the clinical characteristics of jaundice,fever,erythema,splenomegaly,progressive hemocytopenia,liver failure,quantities of abnormal cells in bone marrow,and associated HLH.The immunophenotypes of abnormal cells were positive for CD2,cCD3,CD7,CD56,CD38 and negative for sCD3,CD8 and CD117.The diagnosis of ANKL complicated with HLH was confirmed.Following the initial diagnosis and supplementary treatment,the patient received chemotherapy with VDLP regimen(vincristine,daunorubicin,L-asparaginase and prednisone).However,the patient had severe adverse reactions and complication such as severe hematochezia,neutropenia,and multiple organ dysfunction syndrome,and died a few days later.CONCLUSION This is the first reported case of ANKL with rare skin lesions as an earlier manifestation and associated with HLH.

Revolutionizing gastric cancer treatment:The potential of immunotherapy

Gastric cancer,a prevalent malignancy worldwide,ranks sixth in terms of frequency and third in fatality,causing over a million new cases and 769000 annual deaths.Predominant in Eastern Europe and Eastern Asia,risk factors include family medical history,dietary habits,tobacco use,Helicobacter pylori,and Epstein-Barr virus infections.Unfortunately,gastric cancer is often diagnosed at an advanced stage,leading to a grim prognosis,with a 5-year overall survival rate below 5%.Surgical intervention,particularly with D2 Lymphadenectomy,is the mainstay for early-stage cases but offers limited success.For advanced cases,the National Comprehensive Cancer Network recommends chemotherapy,radiation,and targeted therapy.Emerging immunotherapy presents promise,especially for unresectable or metastatic cases,with strategies like immune checkpoint inhibitors,tumor vaccines,adoptive immunotherapy,and nonspecific immunomodulators.In this Editorial,with regards to the article“Advances and key focus areas in gastric cancer immunotherapy:A comprehensive scientometric and clinical trial review”,we address the advances in the field of immunotherapy in gastric cancer and its future prospects.

Establishment of a prognostic model related to tregs and natural killer cells infiltration in bladder cancer

BACKGROUND Regulatory T cells(Tregs)and natural killer(NK)cells play an essential role in the development of bladder urothelial carcinoma(BUC).AIM To construct a prognosis-related model to judge the prognosis of patients with bladder cancer,meanwhile,predict the sensitivity of patients to chemotherapy and immunotherapy.METHODS Bladder cancer information data was obtained from The Cancer Genome Atlas and GSE32894.The CIBERSORT was used to calculate the immune score of each sample.Weighted gene co-expression network analysis was used to find genes that will have the same or similar expression patterns.Subsequently,multivariate cox regression and lasso regression was used to further screen prognosis-related genes.The prrophetic package was used to predict phenotype from gene expression data,drug sensitivity of external cell line and predict clinical data.RESULTS The stage and risk scores are independent prognostic factors in patients with BUC.Mutations in FGFR3 lead to an increase in Tregs percolation and affect the prognosis of the tumor,and additionally,EMP1,TCHH and CNTNAP3B in the model are mainly positively correlated with the expression of immune checkpoints,while CMTM8,SORT1 and IQSEC1 are negatively correlated with immune checkpoints and the high-risk group had higher sensitivity to chemotherapy drugs.CONCLUSION Prognosis-related models of bladder tumor patients,based on Treg and NK cell percolation in tumor tissue.In addition to judging the prognosis of patients with bladder cancer,it can also predict the sensitivity of patients to chemotherapy and immunotherapy.At the same time,patients were divided into high and low risk groups based on this model,and differences in genetic mutations were found between the high and low risk groups.

Harnessing cytokine-induced killer cells to accelerate diabetic wound healing:an approach to regulating post-traumatic inflammation

Impaired immunohomeostasis in diabetic wounds prolongs infiammation and cytokine dysfunction,thus,delaying or pre-venting wound-surface healing.Extensive clinical studies have been conducted on cytokine-induced killer(CIK)cells recently,as they can be easily proliferated using a straightforward,inex-pensive protocol.Therefore,the function of CIK cells in regulat-ing inflammatory environments has been drawing attention for clinical management.Throughout the current investigation,we discovered the regenerative capacity of these cells in the chal-lenging environment of wounds that heal poorly due to diabe-tes.We demonstrated that the intravenous injection of CIK cells can re-establish a proregenerative inflammatory microenviron-ment.promote larizationand.ultimatel accelerateskin healing in diabetic mice.The results indicated that CIK cell treatment affects macrophage polarization and restores the function regenerative cells under hyperglycemic conditions.This novel cellular therapy offers a promising intervention for clinical applic tions through specific inflammatory regulation functions.

Increasing the frequency of CIK cells adoptive immunotherapy may decrease risk of death in gastric cancer patients

AIM: To analyze the correlation between cytokineinduced killer (CIK) cells adoptive immunotherapy and cancer-related death in gastric cancer patients. METHODS: One hundred and fifty-six gastric cancer patients after operation at the Third Affiliated Hospital of Soochow University were enrolled in this study. Their clinical data including demographic characteristics, operation time, tumor size, pathological type and staging, tumor metastasis, outcome of chemotherapy or CIK cells adoptive immunotherapy, survival time or time of death were collected with a standard structured questionnaire. Kaplan-Meier method was used to estimate the median survival time, and the 2- and 5- year survival rates. Hazard risk (HR) and 95% confidence interval (95% CI) of CIK cells adoptive immunotherapy for gastric cancer were calculated using the two-stage time-dependent covariates Cox model. RESULTS: The survival time of gastric cancer patients was longer after CIK cells adoptive immunotherapy than after chemotherapy (χ 2 = 10.907, P = 0.001). The median survival time of gastric cancer patients was also longer after CIK cells adoptive immunotherapy than after chemotherapy (49 mo vs 27 mo, P < 0.05). The 2- and 5-year survival rates of gastric cancer patients were significantly higher after CIK cells adoptive immunotherapy than after chemotherapy (73.5% vs 52.6%, 40.4% vs 23.9%, P < 0.05). A significant difference was observed in the survival curve for patients who received CIK cells adoptive immunotherapy (0, 1-10, 11-25, and over 25 frequencies) (χ 2 = 14.534, P = 0.002). The frequencies of CIK cells adoptive immunotherapy were significantly related with the decreasing risk of death in gastric cancer patients after adjustment for sex and age of the patients, tumor stage and relapse (HR = 0.54, 95% CI: 0.36-0.80) when the first stage Cox model was used to define the subjects who remained alive beyond 36 mo as survivors. However, no correlation was observed between the frequencies of death in CIK cells adoptive immunotherapy and the risk of gastric cancer patients (HR = 1.09, 95% CI: 0.63-0.89) when the second stage Cox model was used to define the subjects who survived for more than 36 mo as survivors. CONCLUSION: The survival time of the gastric cancer patients treated with chemotherapy combined with CIK cells adoptive immunotherapy is significantly longer than that of the patients treated with chemotherapy alone and increasing the frequency of CIK cells adoptive immunotherapy seems to benefit patients more.

A randomized controlled trial of postoperative tumor lysate-pulsed dendritic cells and cytokine-induced killer cells immunotherapy in patients with localized and locally advanced renal cell carcinoma

Background It remains a challenge to inhibit the local recurrence or distant metastasis of localized or locally advanced renal cell carcinoma （RCC） after surgical resection. We investigated the feasibility, safety and efficacy of immunotherapy using autologous tumor lysate （TL）-pulsed dendritic cells （DCs） and cytokine-induced killer （CIK） cells in patients with localized or locally advanced RCC.

Emergence of immunotherapy as a novel way to treat hepatocellular carcinoma

Tumor immunity proceeds through multiple processes, which consist of antigen presentation by antigen presenting cells(APCs) to educate effector cells and destruction by the effector cytotoxic cells. However, tumor immunity is frequently repressed at tumor sites. Malignantly transformed cells rarely survive the attack by the immune system, but cells that do survive change their phenotypes to reduce their immunogenicity. The resultant cells evade the attack by the immune system and form clinically discernible tumors. Tumor microenvironments simultaneously contain a wide variety of immune suppressive molecules and cells to dampen tumor immunity. Moreover, the liver microenvironment exhibits immune tolerance to reduce aberrant immune responses to massively-exposed antigens via the portal vein, and immune dysfunction is frequently associated with liver cirrhosis, which is widespread in hepatocellular carcinoma(HCC) patients. Immune therapy aims to reduce tumor burden, but it is also expected to prevent non-cancerous liver lesions from progressing to HCC, because HCC develops or recurs from noncancerous liver lesions with chronic inflammatory states and/or cirrhosis and these lesions cannot be cured and/or eradicated by local and/or systemic therapies. Nevertheless, cancer immune therapy should augment specific tumor immunity by using two distinct measures: enhancing the effector cell functions such as antigen presentation capacity of APCs and tumor cell killing capacity of cytotoxic cells, and reactivating the immune system in immune-suppressive tumor microenvironments. Here, we will summarize the current status and discuss the future perspective on immune therapy for HCC.