Feasibility of combination of Gun-Chil-Jung and cytokine-induced killer cells-based immunotherapy for terminal hepatocellular carcinoma patient: a case report.

Introduction: Terminal-stage hepatocellular carcinoma (HCC) is inoperable and currently has no form of adjuvant therapy. This study examined the anticancer herbal extract Gun-Chil-Jung (GCJ) combined with cytokine-induced killer (CIK)-cell-based immunotherapy as a palliative therapy for terminal HCC. We report the case of an HCC patient with extended overall survival and improved symptoms and tumor marker levels following combination therapy with GCJ and CIK cell-based immunotherapy. Baseline Characteristics: From March to July 2020, a 57-year-old man who had been diagnosed with HCC underwent combination treatment with GCJ and CIK cell-based immunotherapy. By August 2021, he was prescribed GCJ. After treatment, the patient's condition was evaluated with respect to overall survival, tumor markers, symptoms, abdominal computed tomography findings, chest x-ray results, and Eastern Cooperative Oncology Group (ECOG) grade. Results: The patient's overall survival, tumor marker levels, ECOG grade, and symptoms, including ascites, lower limb edema, jaundice, pleural effusion, and fatigue, were largely alleviated. Conclusion: We expect that this combination therapy may be an option for palliative therapy of terminal HCC.

Long-term survival after immunotherapy and targeted therapy without chemotherapy in an elderly patient with HER2-positive gastroesophageal junction cancer: A case report.

A 74-yr-old man underwent thoracic laparoscopy combined with radical gastrectomy, and the postoperative pathological diagnosis was esophageal and gastric cardia cancer pT3N1M0, pStage IIB. Immunohistochemical staining for HER2 (3+) and PD-L1 (<5%) was positive. Adjuvant chemotherapy was not performed because the patient developed severe thrombocytopenia (platelet counts <30 × 109/L), which was never cured throughout the reporting period. At 10.7 months post-surgery, he suffered metastases in multiple organs, including the peritoneum, liver, lung, and bone. Following two cycles of first-line trastuzumab and pembrolizumab (200 mg), he developed immune-related myositis (G2), myocarditis (G2), and hepatitis (G1). Therefore, pembrolizumab was discontinued. Trastuzumab was administered as a monotherapy; meanwhile, adoptive cytokine-induced killer (CIK) cell infusions were initiated. Eight months after the initial immunotherapy, a solitary brain metastasis was detected, and the patient underwent CyberKnife radiosurgery. For second-line therapy, adoptive CIK cell immunotherapy plus trastuzumab was still used. At the time of reporting, the patient had achieved a complete response (CR) in the brain and liver and a partial response (PR) in the ilium, and he had been followed-up for 36.6 months, much longer than the median survival time for patients with advanced GEJ cancer. We suggest that HER2-targeted therapy and immunotherapy with pembrolizumab or CIK adoptive cell infusions prolonged the overall survival of an elderly patient with HER2-positive GEJ cancer with multiple metastases.

Efficacy of Cytokine-Induced Killer Cell Immunotherapy for Patients With Pathologically Pure Glioblastoma.

The most common malignant central nervous system tumor is glioblastoma multiforme (GBM). Cytokine-induced killer (CIK) cell therapy is a promising type of adoptive cell immunotherapy for various cancers. We previously conducted a randomized clinical trial on CIK cell therapy in patients with GBM. The aim of this study was to evaluate the efficacy of CIK immunotherapy for patients with pathologically pure GBM, using data from our previous randomized clinical trial. The difference between overall survival (OS) and progression-free survival (PFS) according to CIK immunotherapy was analyzed using the Kaplan-Meier method. Hazard ratios were calculated using univariate and multivariate Cox regression analyses to determine whether CIK cell immunotherapy was independently associated with higher OS and PFS in patients with pure GBM. A total of 156 eligible patients were included in the modified intention-to-treat (mITT) population. We confirmed that 125 (80.1%) GBM samples were pure GBM tumors without the presence of other types of tumors. For patients with pure GBM, Kaplan-Meier analysis showed no significant difference in OS between the CIK cell treatment and control groups. However, multivariate Cox regression demonstrated CIK cell immunotherapy as an independent predictor of greater OS (hazard ratio, 0.59; 95% CI, 0.36-0.97; p = 0.038) and PFS (hazard ratio, 0.55; 95% CI, 0.36-0.84; p = 0.001) in patients with pathologically pure GBM in the mITT population. This study showed that CIK cell immunotherapy combined with conventional temozolomide chemoradiotherapy could prolong OS and PFS in patients with newly diagnosed pathologically pure GBM, with no significant adverse events related to treatment. However, unlike the results of multivariate Cox analysis, no statistical significance of CIK cell immunotherapy in OS in Kaplan-Meier analysis raises a question. Further studies are required to validate these results.

Case Report: Chemotherapy and Radiotherapy Combined With DC-CIK for Pulmonary and Mediastinal Metastases From Nasopharyngeal Carcinoma.

INTRODUCTION: The optimal treatment for pulmonary and mediastinal metastasis of nasopharyngeal carcinoma (NPC) is still controversial, and the therapeutic effect is poor recently. In one case, we demonstrated a long-term survival after postoperative chemoradiotherapy combined with dendritic cell and cytokine-induced killer (DC-CIK) immunotherapy for pulmonary and mediastinal metastases from NPC. BASELINE CHARACTERISTICS: A 53-year-old woman was admitted to our hospital in June 2008. Pathological biopsy revealed a poorly differentiated squamous cell carcinoma located in the nasopharynx with the invasion of internal pterygoid muscles, the sphenoid bone, and unilateral neck lymph node metastasis. No distant metastases were observed. The stage of NPC was T3N1M0 III (AJCC8). The patient received concurrent chemoradiotherapy for primary lesion and neck lymph nodes and achieved complete remission (CR) of the disease after 3 months. Follow-up at 3-month intervals was carried out. Pulmonary and mediastinal lymph node metastases were found in July 2009. The patient then underwent right upper lobectomy and mediastinal lymph node dissection and five cycles of gemcitabine and cisplatin (GP) regimen chemotherapy, following radiotherapy and DC-CIK immunotherapy. RESULTS: After a follow-up time of 13 years, no tumor recurrence or metastasis and severe adverse reactions were found. CONCLUSION: Postoperative chemotherapy and radiotherapy in combination with DC-CIK immunotherapy may produce a synergistic therapeutic effect on patients with mediastinal lymph node metastasis from NPC.

Cytokine-induced killer cells mediated pathways in the treatment of colorectal cancer.

Cytokine-induced killer (CIK) cell therapy is a type of adoptive immunotherapy that due to its high proliferation rate and anti-tumor characteristics, is being investigated to treat various solid tumors. Since advanced colorectal cancer (CRC) has high mortality and poor survival rates, and the efficacy of chemotherapy and radiotherapy is limited in treatment, the application of CIK cell therapy in CRC has been evaluated in numerous studies. This review aims to summarize the clinical studies that investigated the safety and clinical efficacy of CIK cell therapy in CRC. Therefore, 1,969 enrolled CRC patients in the clinical trials, of which 842 patients received CIK cells in combination with chemotherapy with or without dendritic cell (DC) infusions, were included in the present review. Furthermore, the signaling pathways involved in CIK cell therapy and novel methods for improving migration abilities are discussed. Video abstract.

Cost-Effectiveness of Adjuvant Immunotherapy With Cytokine-Induced Killer Cell for Hepatocellular Carcinoma Based on a Randomized Controlled Trial and Real-World Data.

BACKGROUND: Studies using data from randomized controlled trials (RCTs) and real-world data (RWD) have suggested that adjuvant cytokine-induced killer (CIK) cell immunotherapy after curative treatment for hepatocellular carcinoma (HCC) prolongs recurrence-free survival (RFS) and overall survival (OS). However, the cost-effectiveness of CIK cell immunotherapy as an adjuvant therapy for HCC compared to no adjuvant therapy is uncertain. METHODS: We constructed a partitioned survival model to compare the expected costs, life-year (LY), and quality-adjusted life-year (QALY) of a hypothetical population of 10,000 patients between CIK cell immunotherapy and no adjuvant therapy groups. Patients with HCC aged 55 years who underwent a potentially curative treatment were simulated with the model over a 20-year time horizon, from a healthcare system perspective. To model the effectiveness, we used OS and RFS data from RCTs and RWD. We estimated the incremental cost-effectiveness ratios (ICERs) and performed extensive sensitivity analyses. RESULTS: Based on the RCT data, the CIK cell immunotherapy incrementally incurred a cost of $61,813, 2.07 LYs, and 1.87 QALYs per patient compared to no adjuvant therapy, and the estimated ICER was $33,077/QALY. Being less than the willingness-to-pay threshold of $50,000/QALY, CIK cell immunotherapy was cost-effective. Using the RWD, the ICER was estimated as $25,107/QALY, which is lower than that obtained using RCT. The time horizon and cost of productivity loss were the most influential factors on the ICER. CONCLUSION: We showed that receiving adjuvant CIK cell immunotherapy was more cost-effective than no adjuvant therapy in patients with HCC who underwent a potentially curative treatment, attributed to prolonged survival, reduced recurrence of HCC, and better prognosis of recurrence. Receiving CIK cell immunotherapy may be more cost-effective in real-world clinical practice.

Immune evasion by cancer stem cells.

Tumor immunity represents a new avenue for cancer therapy. Immune checkpoint inhibitors have successfully improved outcomes in several tumor types. In addition, currently, immune cell-based therapy is also attracting significant attention. However, the clinical efficacy of these treatments requires further improvement. The mechanisms through which cancer cells escape the immune response must be identified and clarified. Cancer stem cells (CSCs) play a central role in multiple aspects of malignant tumors. CSCs can initiate tumors in partially immunocompromised mice, whereas non-CSCs fail to form tumors, suggesting that tumor initiation is a definitive function of CSCs. However, the fact that non-CSCs also initiate tumors in more highly immunocompromised mice suggests that the immune evasion property may be a more fundamental feature of CSCs rather than a tumor-initiating property. In this review, we summarize studies that have elucidated how CSCs evade tumor immunity and create an immunosuppressive milieu with a focus on CSC-specific characteristics and functions. These profound mechanisms provide important clues for the development of novel tumor immunotherapies.

High Complete Response Rate in Patients With Metastatic Renal Cell Carcinoma Receiving Autologous Cytokine-Induced Killer Cell Therapy Plus Anti-Programmed Death-1 Agent: A Single-Center Study.

Background and Objective: The results of the CheckMate 025 trial established the status of nivolumab in the second-line treatment of metastatic renal cell carcinoma (mRCC), with an objective response rate (ORR) of 25% and a complete response (CR) rate of 1%. Thus, the efficacy of anti-programmed death (PD)-1 antibodies in the second-line treatment of mRCC requires improvement. The purpose of this study was to explore the clinical efficacy and safety of anti-PD-1 agents combined with cytokine-induced killer (CIK) cell therapy for refractory mRCC. Patients and Methods: Patients with mRCC refractory to previous targeted therapy were included in this study. All patients received anti-PD-1 plus CIK cell therapy. The ORR and CR rate, progression-free survival (PFS), overall survival (OS), and safety were assessed. Results: CR was observed in seven of the 29 patients, and partial response was observed in five patients. The ORR was 41.4% and the median PFS was 15.0 months. Up to the last follow-up, 15 patients died with an average survival time of 37 months. Among the patients who achieved a CR, one experienced cerebellar metastasis 18.8 months after discontinuation, but achieved CR again after localized gamma knife and 1-month axitinib treatment. This regimen was tolerated well and there was no treatment-related death. Conclusions: Combination therapy with anti-PD-1 and CIK cell therapy is safe and effective in patients with mRCC refractory to previous targeted therapy. The high CR rate and long disease-free survival even after long-term discontinued therapy suggest that this combination treatment may represent a potential curative regimen for this type of malignancy.

Clinical efficacy of intra-cavitary infusions of autologous dendritic cell/cytokine-induced killer cell products for the treatment of refractory malignant pleural effusions and ascites.

To explore the safety and efficacy of intra-cavitary infusions of autologous mixed dendritic cell (DC)-cytokine-induced killer (CIK) cell products in advanced cancer patients with malignant pleural effusions or ascites. DC-CIKs were expanded ex vivo (mean yield of 1.36×109 cells (range, 0.74~4.98×109)) from peripheral blood mononuclear cells obtained by repeated venipuncture or apheresis. Patients received at least 1 cycle of 3 infusions of the DC-CIKs administered by indwelling catheter into the pleural or peritoneal cavity every other day. The volume of malignant effusions was assessed radiologically. Peripheral blood lymphocyte populations were enumerated by flow cytometry. Quality of life (QoL) during the DC-CIK infusions was assessed by the EORTC QLQ-30 instrument. ctDNA sequencing was performed to analyze gene clonal load and molecular tumor burden during the infusion treatment. Thirty-seven patients with breast, lung and other malignancies were enrolled. The results showed that intra-cavitary DC-CIK infusions (16 intrapleural and 21 intraperitoneal) were well-tolerated with no grade 3/4 adverse events. There was one complete response with effusion disappearance (CR) (3%), 13 partial responses (PR) (35%), 12 with stable disease (SD) (32%) and 11 with progressive disease (PD) (30%), resulting in a clinical effusion control rate (CCR) of 70% (26/37). The total number of infused CIKs and the CD3+/CD8+ and CD8+/CD28+ T cell frequencies within the CIKs were associated with effusion control (P=0.013). Moreover, increased peripheral blood CD3+/CD8+ (P=0.035) and decreased CD4+/CD25+ T cell frequencies (P=0.041) following the DC-CIK infusions were associated with malignant effusion and ascites control. Reductions in ctDNA correlated with clinical benefit. In conclusion, intra-cavitary autologous cellular immunotherapy is an alternative method to effectively control malignant pleural effusions and ascites. The overall effusion control rate was associated with higher peripheral blood effector T cell frequencies.

Cytokine-induced Killer T Cells Enhance the Cytotoxicity Against Carboplatin-resistant Ovarian Cancer Cells.

BACKGROUND/AIM: Ovarian cancer (OC) is typically diagnosed at an advanced stage with limitations for cure. Cytokine-induced killer (CIK) T cell therapy exerts significant cytotoxic effects against cancer cells and reduces the adverse effects of chemotherapy. Herein, we performed a flow cytometry-based method to evaluate the cytotoxicity of peripheral blood mononuclear cells-derived CIK cells against OC cells. MATERIALS AND METHODS: The CIK cells were induced and expanded using an interferon-γ/IL-2-based xeno-free medium system. The cytotoxicity of CIK cells or carboplatin against OC cells was examined. RESULTS: The CIK cells showed an NK-like phenotypic characteristic and dose-dependently increased cytotoxicity against OC cells. We found that the number of advanced OC cells, which were more resistant to carboplatin, was dramatically decreased by an additional one-shot CIK treatment. CONCLUSION: CIK cells have a potent cytotoxic ability that would be explored as an alternative strategy for cancer treatment in the near future.

Antigen-independent killer cells prepared for adoptive immunotherapy: One source, divergent protocols, diverse nomenclature.

Adoptive cell therapy (ACT) using tumor antigen-independent killer cells has been widely used in clinical trials of cancer treatment. Circumventing the need for identification of a particular tumor-associated antigen on tumor cells, the approach has opened possibilities for the extension of ACT immunotherapy to patients with a wide variety of cancer types. Namely, Natural Killer (NK), Lymphokine-activated Killer (LAK) cells and Cytokine-induced killer (CIK) cells are the most commonly used cell types in antigen-independent adoptive immunotherapy of cancer. They all originate from peripheral blood mononuclear cells and share several common features in their killing mechanisms. However, despite broad application in clinical settings, the boundaries between these cell types are not very clearly defined. The current study aims to review different aspects of these cell populations in terms of phenotypical characteristic and preparation media, to clarify how the boundaries are set.

Predictive significance of T cell subset changes during ex vivo generation of adoptive cellular therapy products for the treatment of advanced non-small cell lung cancer.

Adoptive T cell immunotherapy with cytokine-induced killer cells (CIKs) has been demonstrated to prolong the survival of patients with advanced non-small cell lung cancer (NSCLC). The aim of the present study was to evaluate whether the expansion of effector T cells and the decrease of regulatory T cells (Tregs) that occurred during the ex vivo generation of DC-CIKs were associated with improved clinical outcome in patients who received treatment. CIKs were generated ex vivo over a 28-day period from the peripheral blood apheresis product of 163 patients with advanced cancer (including 30 with NSCLC). CIKs were also generated from an additional cohort of 65 patients with NSCLC over a 15-day period. The progression-free survival (PFS) and overall survival (OS) time of patients treated with CIKs was determined by reviewing the patients' medical records. The number of CIKs gradually increased during the culture period and peaked at day 15, followed by a slight decline until day 28. Similarly, the percentages of T cell subtypes associated with anti-tumor activity (CD3+, CD3+CD4+, CD3+CD8+ and CD8+CD28+) peaked at day 15. Although the percentage of CD4+CD25+CD127+ Tregs increased by day 7, a decrease was subsequently observed. Among the 95 patients with NSCLC, those with a post/pre-culture ratio of CD8+CD28+ T lymphocytes >2.2 had significantly better PFS and OS compared with those with ratios ≤2.2. Those with a post/pre-culture CD4+CD25+CD127+ Treg ratio ≤0.6 had significantly better OS and PFS compared with those with ratios >0.6. The peak expansion of CIKs from peripheral blood mononuclear cells occurred at day 15 of ex vivo culture. PFS and OS were associated with post/pre-culture CD8+CD28+ T lymphocyte ratio >2.2 and post/pre-culture CD4+CD25+CD127+ Treg ratio <0.6 in the CIKs of patients with advanced NSCLC treated with adoptive T cell immunotherapy. Further efforts are underway to optimize the DC-CIK infusion for cancer immunotherapy.

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.

Efficacy of cytokine-induced killer cell-based immunotherapy for hepatocellular carcinoma.

In attempts to delay tumor progression after surgery or minimally invasive local treatments, multidisciplinary strategies have been broadly studied in patients with hepatocellular carcinoma (HCC). The objective of this present study was to evaluate the efficacy of autologous transplantations of cytokine-induced killer (CIK) cells as an adjuvant therapy for patients with HCC. A total of 264 patients with HCC were enrolled in this retrospective study. Of these patients, 165 received either CIK cell therapy alone or as adjuvant therapy to surgery, transcatheter arterial chemoembolization (TACE), or TACE-based comprehensive treatments (CT). The remaining 99 patients received only surgery or TACE. Kaplan-Meier analysis and the Chi-squared test were used to analyze the overall survival (OS), progression-free survival (PFS), and clinical characteristics of the patients in the different treatment subgroups. Kaplan-Meier analysis suggested that patients in the Surgery+CIK group had a significantly improved OS compared with those in the other three groups (P < 0.001). Furthermore, patients who developed a fever after the CIK cell treatments manifested a likely better OS (P = 0.028). Subgroup analysis indicated that patients in the Surgery+CIK group likely had an improved PFS but a similar OS compared with the patients in the Surgery-alone group (P = 0.055 for PFS, and P = 0.746 for OS). Further subgroup analysis showed that the OS in both the TACE+CIK and CT+CIK groups was prolonged significantly compared with that in the TACE-alone group (P = 0.015 and P = 0.018, respectively). However, similar OS was observed between the TACE+CIK and CT+CIK groups (P = 0.686). Autologous transplantation of CIK cells as an adjuvant therapy was associated with better survival for patients with HCC, especially for those who had also undergone TACE. A fever reaction might be a potential event for assessing the curative effect of the CIK treatment.

Adjuvant cytokine-induced killer cell immunotherapy for hepatocellular carcinoma: a propensity score-matched analysis of real-world data.

BACKGROUND: Several randomized controlled trials have shown that adjuvant immunotherapy with autologous cytokine-induced killer (CIK) cells prolongs recurrence-free survival (RFS) after curative treatment for hepatocellular carcinoma (HCC). We investigated the efficacy of adjuvant immunotherapy with activated CIK cells in real-world clinical practice. METHODS: A total of 59 patients who had undergone curative surgical resection or radiofrequency ablation for stage I or II HCC, and subsequently received adjuvant CIK cell immunotherapy at two large-volume centers in Korea were retrospectively included. Propensity score matching with a 1:1 ratio was conducted to avoid possible bias, and 59 pairs of matched control subjects were also generated. The primary endpoint was RFS and the secondary endpoints were overall survival and safety. RESULTS: The median follow-up duration was 28.0 months (interquartile range, 22.9-42.3 months). In a univariable analysis, the immunotherapy group showed significantly longer RFS than the control group (hazard ratio [HR], 0.42; 95% CI, 0.22-0.80; log-rank P = 0.006). The median RFS in the control group was 29.8 months, and the immunotherapy group did not reach a median RFS. A multivariable Cox proportional hazard analysis showed that immunotherapy was an independent predictor for HCC recurrence (adjusted HR, 0.38; 95% CI, 0.20-0.73; P = 0.004). The overall incidence of adverse events in the immunotherapy group was 16/59 (27.1%) and no patient experienced a grade 3 or 4 adverse event. CONCLUSIONS: The adjuvant immunotherapy with autologous CIK cells after curative treatment safely prolonged the RFS of HCC patients in a real-world setting.

Immune cell therapy for hepatocellular carcinoma.

Given the success of immune checkpoint inhibitors and chimeric antigen receptor (CAR) T cells in clinical settings, the host immune system plays an important role in the recognition and targeting of tumor cells in cancer immunotherapy. As a result, there have been numerous advancements in immune cell therapy using human immune cells. However, recent evidence suggests that one type of immunotherapy alone is not effective for the treatment of cancer, particularly solid tumors. Thus, effective immunotherapy combinations, such as the combination of checkpoint inhibitors and immune cell therapy, are needed. This review focuses on hepatocellular carcinoma among other solid tumors and discusses the current status and future of immune cell therapy in cancer immunotherapy.

Sustained efficacy of adjuvant immunotherapy with cytokine-induced killer cells for hepatocellular carcinoma: an extended 5-year follow-up.

Our earlier multicenter randomized controlled trial showed that adjuvant immunotherapy with cytokine-induced killer (CIK) cells resulted in longer recurrence-free survival (RFS) and overall survival (OS) as well in patients who received curative treatment for hepatocellular carcinoma (HCC). In the present study, we determined if the efficacy of CIK cell therapy continued after end of repeated CIK cell injections. We performed a follow-up study of our preceding trial. We included 226 patients: 114 patients in the immunotherapy group (injection of 6.4 × 109 CIK cells, 16 times during 60 weeks) and 112 patients in the control group (no treatment) after potentially curative treatment for HCC. In total, 162 patients (89 of the immunotherapy group and 73 of controls) underwent an extended follow-up for 60 months after randomization of the last patient. The primary endpoint was RFS, and secondary endpoints included OS. During follow-up time of median 68.5 months (interquartile range 45.0-82.2 months), the immunotherapy group continued to show a significantly lower risk of recurrence or death [hazard ratio (HR) 0.67; 95% confidence interval (CI) 0.48-0.94; P = 0.009 by one-sided log-rank test]. At 5 years, RFS rate was 44.8% in the immunotherapy group and 33.1% in the control group. The risk of all-cause death was also lower in the immunotherapy group compared to the control group (HR 0.33; 95% CI 0.15-0.76; P = 0.006). In patients who received curative treatment for HCC, the significant improvement in RFS and OS as a result of adjuvant CIK cell immunotherapy lasted over 5 years without boosting.

Chemotherapy combined with dendritic cell vaccine and cytokine-induced killer cells in the treatment of colorectal carcinoma: a meta-analysis.

AIM: To investigate the efficacy and safety of dendritic cell (DC) vaccine combined with cytokine-induced killer (CIK) cell therapy in colorectal carcinoma (CRC). PATIENTS AND METHODS: PubMed, Embase, and Cochrane Library databases were searched systematically for clinical trials of DC vaccine and CIK cell therapy combined with chemotherapy for CRC. The primary and secondary endpoints were overall survival (OS) and disease-free survival (DFS), respectively. Pooled risk ratios were used to assess the treatment efficacy. Both random and fixed effects models were used for statistical analysis. The study population consisted of 871 CRC patients enrolled in four trials. RESULTS: OS and DFS were significantly improved in patients who received chemotherapy combined with DC vaccine and CIK cells, and no severe adverse events were shown. CONCLUSIONS: The study demonstrated that the addition of DC vaccine and CIK cell therapy to chemotherapy is feasible and effective in patients with CRC.

Cytokine-induced killer cell therapy as a promising adjunctive immunotherapy for multidrug-resistant pulmonary TB: a case report.

In this report, we identified a multidrug-resistant tuberculosis (MDR-TB) patient who remained acid-fast bacilli culture positive despite aggressive WHO-directed therapy. Between July 2014 and February 2015, she received eight courses of cytokine-induced killer (CIK) cell-based adoptive cellular immunotherapy in combination to the second-line anti-TB treatment. This case achieved culture conversion, and experienced no relapse during 2-year follow-up under the treatment with CIK cell-based adoptive cellular immunotherapy. Our data indicate that CIK immunotherapy is a promising adjunctive therapeutic method for improving the efficacy combined with the second-line anti-TB regimens against MDR-TB. Randomized trials are warranted to confirm the efficacy and safety of adjunctive CIK therapy in patients infected with MDR-TB.

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 non-cancerous 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.