• chimeric antigen receptor (CAR)
• cytokine-induced killer (CIK) cells
• donor lymphocyte infusion (DLI)
• graft versus leukemia (GVL)
• hematopoietic cell transplant
• leukemia

• Humans
• Graft vs Host Disease/immunology
• Graft vs Leukemia Effect/immunology
• Hematopoietic Stem Cell Transplantation/adverse effects
• Hematopoietic Stem Cell Transplantation/methods
• Cytokine-Induced Killer Cells/immunology
• Transplantation, Homologous
• Animals
• Immunotherapy, Adoptive/methods

• CAR
• NK cells
• cancer
• genetic engineering
• immunotherapy

• Humans
• Killer Cells, Natural/immunology
• Neoplasms/therapy
• Neoplasms/immunology
• Immunotherapy, Adoptive/methods
• Animals
• Tumor Microenvironment/immunology
• Gene Editing
• Cellular Reprogramming/immunology
• Receptors, Chimeric Antigen/immunology
• Receptors, Chimeric Antigen/genetics
• Clinical Trials as Topic

• CIK cell
• Cancer
• Hematologic malignancies
• Therapy

• Humans
• Cytokine-Induced Killer Cells/immunology
• Hematologic Neoplasms/therapy
• Hematologic Neoplasms/immunology
• Immunotherapy, Adoptive/methods
• Immunotherapy/methods

• Cancer
• Expansion
• Hematological malignancies
• Immunotherapy
• Natural killer

• Humans
• K562 Cells
• Killer Cells, Natural
• Immunotherapy
• Feeder Cells
• Hematologic Neoplasms

• immunotherapy
• lung neoplasms
• melanoma
• sarcoma

• Animals
• Combined Modality Therapy
• Epitopes
• Immunotherapy/methods
• Mice
• Neoplasms/therapy
• Toll-Like Receptor 3

• F30 CA221268 NCI NIH HHS
• German Ministry of Education and Research
• Frauke Weiskam + Christel Ruranski Stiftung
• Nachwuchsforschungsgruppen NRW
• National Cancer Institute
• Deutsche Krebshilfe
• Thyssen Foundation
• Deutsche Forschungsgemeinschaft
• Else Kröner-Fresenius Stiftung
• National Heart, Lung, and Blood Institute
• German-Israeli Foundation for Research and Development

Natural killer (NK) cells have played a critical—if largely unrecognized or ignored—role in the treatment of B cell non-Hodgkin lymphoma (NHL) since the introduction of CD20-directed immunotherapy with rituximab as a cornerstone of therapy over 25 years ago. Engagement with NK cells leading to lysis of NHL targets through antibody-dependent cellular cytotoxicity (ADCC) is a critical component of rituximab’s mechanism of action. Despite this important role, the only aspect of B cell NHL therapy that has been adopted as standard therapy that even indirectly augments or restores NK cell function is the introduction of obinutuzumab, a CD20 antibody with enhanced ability to engage with NK cells. However, over the last 5 years, adoptive immunotherapy with effector lymphocytes of B cell NHL has experienced tremendous growth, with five different CAR T cell products now licensed by the FDA, four of which target CD19 and have approved indications for some subtype of B cell NHL—axicabtagene ciloleucel, brexucabtagene autoleucel, lisocabtagene maraleucel, and tisagenlecleucel. These T cell-based immunotherapies essentially mimic the recognition, activation pathway, and cytotoxic machinery of a CD19 antibody engaging NK cells and lymphoma targets. Despite their efficacy, these T cell-based immunotherapies have been difficult to implement because they require 4–6 weeks of manufacture, are costly, and have significant toxicities. This renewed interest in the potential of cellular immunity—and the manufacturing, supply chain, and administration logistics that have been addressed with these new agents—have ignited a new wave of enthusiasm for NK cell-directed therapies in NHL. With high safety profiles and proven anti-lymphoma efficacy, one or more new NK cell-directed modalities are certain to be introduced into the standard toolbox of NHL therapy within the next few years, be it function-enhancing cytokine muteins, multi-domain NK cell engagers, or adoptive therapy with expanded or genetically modified NK cells.

• Antibody-dependent direct cytotoxicity
• Chimeric antigen receptor
• NK cells
• Non-Hodgkin lymphoma

Lymphoma is a heterogeneous group of neoplasms including over 70 different subtypes. Its biological characteristic of deriving from lymphoid tissues makes it ideal for immunotherapy. In this paper, we provide insights into lymphoma-specific clinical trials based on cytokine-induced killer (CIK) cell therapy. We also reviewed pre-clinical lymphoma models where CIK cells have been used along with other synergetic tumor-targeting immune modules to improve their therapeutic potential. From a broader perspective, we will highlight that CIK cell therapy has potential, and in this rapidly evolving landscape of cancer therapies its optimization (as a personalized therapeutic approach) will be beneficial in lymphomas.

Cancer is a complex disease where resistance to therapies and relapses often pose a serious clinical challenge. The scenario is even more complicated when the cancer type itself is heterogeneous in nature, e.g., lymphoma, a cancer of the lymphocytes which constitutes more than 70 different subtypes. Indeed, the treatment options continue to expand in lymphomas. Herein, we provide insights into lymphoma-specific clinical trials based on cytokine-induced killer (CIK) cell therapy and other pre-clinical lymphoma models where CIK cells have been used along with other synergetic tumor-targeting immune modules to improve their therapeutic potential. From a broader perspective, we will highlight that CIK cell therapy has potential, and in this rapidly evolving landscape of cancer therapies its optimization (as a personalized therapeutic approach) will be beneficial in lymphomas.

• clinical study
• cytokine-induced killer cells
• immunotherapy
• lymphoma

Dendritic cells (DCs) are immune specialized cells playing a critical role in promoting immune response against antigens, and may represent important targets for therapeutic interventions in cancer. DCs can be stimulated ex vivo with pro-inflammatory molecules and loaded with tumor-specific antigen(s). Protocols describing the specific details of DCs vaccination manufacturing vary widely, but regardless of the employed protocol, the DCs vaccination safety and its ability to induce antitumor responses is clearly established. Many years of studies have focused on the ability of DCs to provide overall survival benefits at least for a selection of cancer patients. Lessons learned from early trials lead to the hypothesis that, to improve the efficacy of DCs-based immunotherapy, this should be combined with other treatments. Thus, the vaccine’s ultimate role may lie in the combinatorial approaches of DCs-based immunotherapy with chemotherapy and radiotherapy, more than in monotherapy. In this review, we address some key questions regarding the integration of DCs vaccination with multimodality therapy approaches for cancer treatment paradigms.

• adjuvant therapy
• cancer
• dendritic cells
• immunotherapy

• Adjuvants, Immunologic/therapeutic use
• Animals
• Antigens, Neoplasm/immunology
• Cancer Vaccines/immunology
• Cancer Vaccines/therapeutic use
• Combined Modality Therapy/methods
• Dendritic Cells/immunology
• Humans
• Immune Checkpoint Inhibitors/therapeutic use
• Immunotherapy, Adoptive/methods
• Neoplasms/drug therapy
• Neoplasms/immunology
• Neoplasms/radiotherapy
• Progression-Free Survival
• Tumor Escape/drug effects
• Tumor Escape/radiation effects

Patients affected by aggressive B-cell malignancies who are resistant to primary or salvage chemoimmunotherapy have an extremely poor prognosis and limited therapeutic options. Promising therapeutic success has been achieved with the infusion of CD19 chimeric antigen receptor-T cells, but several limits still restrain the administration to a limited proportion of patients. This unmet clinical need might be fulfilled by an adoptive immunotherapy approach that combines cytokine-induced killer (CIK) cells and monoclonal antibodies (mAb) to the CD20 antigen. Indeed, CIK cells are an effector population endowed with antitumor activity, which can be further improved and antigen-specifically redirected by clinical-grade mAb triggering antibody-dependent cell-mediated cytotoxicity.

CIK cells were generated from peripheral blood of patients affected by different B-cell malignancies using a blinatumomab-based cell culture protocol. Effector cells were combined with the anti-CD20 mAb obinutuzumab and their therapeutic activity was assessed both in vitro and in vivo.

CIK cells were successfully expanded in clinically relevant numbers, starting from small volumes of peripheral blood with extremely low CD3⁺ counts and high tumor burden. This relied on the addition of blinatumumab in culture, which leads to the simultaneous expansion of effector cells and the complete elimination of the neoplastic component. Moreover, CIK cells were highly cytotoxic in vitro against both B-cell tumor cell lines and autologous neoplastic targets, and had a significant therapeutic efficacy against a B-cell malignancy patient-derived xenograft on in vivo transfer.

The combination of an easily expandable CIK cell effector population with a mAb already in clinical use establishes a tumor antigen-specific redirection strategy that can be rapidly translated into clinical practice, providing an effective therapeutic alternative for B-cell malignancies without any need for genetic modifications. Additionally, the approach can be potentially applied to an extremely vast array of different tumors by simply substituting the targeting mAb.

• adoptive
• combined modality therapy
• hematologic neoplasms
• immunotherapy

• cell therapy
• clinical trials
• immune checkpoint inhibitors (ICIs)
• immunotherapy
• lymphoma

This review is intended to provide an overview on the history and recent advances of T cell and natural killer (NK) cell-based immunotherapy. While the thymus was discovered as the origin of T cells in the 1960s, and NK cells were first described in 1975, the clinical application of adoptive cell therapies (ACT) only began in the early 1980s with the first lymphokine activated killer (LAK) cell product for the treatment of cancer patients. Over the past decades, further immunotherapies have been developed, including ACT using cytokine-induced killer (CIK) cells, products based on the NK cell line NK-92 as well as specific T and NK cell preparations. Recent advances have successfully improved the effectiveness of T, NK, CIK or NK-92 cells towards tumor-targeting antigens generated by genetic engineering of the immune cells. Herein, we summarize the promising development of ACT over the past decades in the fight against cancer.

The promising development of adoptive immunotherapy over the last four decades has revealed numerous therapeutic approaches in which dedicated immune cells are modified and administered to eliminate malignant cells. Starting in the early 1980s, lymphokine activated killer (LAK) cells were the first ex vivo generated NK cell-enriched products utilized for adoptive immunotherapy. Over the past decades, various immunotherapies have been developed, including cytokine-induced killer (CIK) cells, as a peripheral blood mononuclear cells (PBMCs)-based therapeutic product, the adoptive transfer of specific T and NK cell products, and the NK cell line NK-92. In addition to allogeneic NK cells, NK-92 cell products represent a possible “off-the-shelf” therapeutic concept. Recent approaches have successfully enhanced the specificity and cytotoxicity of T, NK, CIK or NK-92 cells towards tumor-specific or associated target antigens generated by genetic engineering of the immune cells, e.g., to express a chimeric antigen receptor (CAR). Here, we will look into the history and recent developments of T and NK cell-based immunotherapy.

• CAR-NK cell
• CAR-T cell
• CIK cell
• NK cell
• NK-92
• T cell
• cell therapy
• immune therapy

The term “cancer stem cells” (CSCs) commonly refers to a subset of tumor cells endowed with stemness features, potentially involved in chemo-resistance and disease relapses. CSCs may present peculiar immunogenic features influencing their homeostasis within the tumor microenvironment. The susceptibility of CSCs to recognition and targeting by the immune system is a relevant issue and matter of investigation, especially considering the multiple emerging immunotherapy strategies. Adoptive cellular immunotherapies, especially those strategies encompassing the genetic redirection with chimeric antigen receptors (CAR), hold relevant promise in several tumor settings and might in theory provide opportunities for selective elimination of CSC subsets. Initial dedicated preclinical studies are supporting the potential targeting of CSCs by cellular immunotherapies, indirect evidence from clinical studies may be derived and new studies are ongoing. Here we review the main issues related to the putative immunogenicity of CSCs, focusing on and highlighting the existing evidence and opportunities for cellular immunotherapy approaches with T and non-T antitumor lymphocytes.

• adoptive immunotherapy
• cancer stem cells (CSCs)
• chimeric antigen receptor (CAR)
• immunotherapy

• Humans
• Immunotherapy/methods
• Neoplastic Stem Cells/immunology
• Tumor Microenvironment

• ADCC
• CAR NK
• KIR
• NK cell
• cellular therapy

• Adoptive cell therapy
• Cytokine-Induced Killer cells
• Immunotherapy
• Serum-free
• ex vivo expansion

• chemokine
• chemokine receptors
• colorectal cancer
• cytokine induce killer cells
• immunotherapy

• SK-N-SH cells
• anti-GD2 antibody
• cell death
• cytokine-induced killer cells
• natural killer cells

• adoptive cell therapy
• cancer immunotherapy
• immune cells
• ovarian cancer

• cancer
• combined modality therapy
• cytokine-induced killer cells
• immunotherapy

To systematically evaluate the efficacy and safety of Cytokine-induced killer cells/dendritic cells-cytokine induced killer cells (CIK/DC-CIK) immunotherapy in treating advanced colorectal cancer (CRC) patients.

29 trials including 2,610 CRC patients were evolved. Compared with chemotherapy alone, the combination of chemotherapy with CIK/DC-CIK immunotherapy significantly prolonged the overall survival rate (OS) and disease-free survival rate (DFS) (1–5 year OS, P < 0.01; 1-, 2-, 3- and 5-year DFS, P < 0.01). The combined therapy also improved patients’ overall response, disease control rate and life quality (P < 0.05). After immunotherapy, lymphocyte subsets percentages of CD3⁺, CD3⁻CD56⁺, CD3⁺CD56⁺ and CD16⁺CD56⁺ (P < 0.01) and cytokines levels of IL-2 and IFN-γ (P < 0.05) were increased, while CD4⁺, CD8⁺ and CD4⁺CD25⁺ and IL-6 and TNF-α did not show significant change (P > 0.05).

Clinical trials reporting response or safety of CIK/DC-CIK immunotherapy treating advanced CRC patients and published before September 2016 were searched in Cochrane Library, EMBASE, PubMed, Wanfang and CNKI database. Research quality and heterogeneity were evaluated before analysis. Pooled analyses were performed using random or fixed-effect models.

The combination of CIK/DC-CIK immunotherapy and chemotherapy prolong CRC patients’ survival time, enhanced patients’ immune function and alleviates the adverse effects caused by chemotherapy.

• colorectal cancer
• cytokine-induced killer cells
• dendritic cells
• immunotherapy
• meta-analysis

• CIK precursor cells
• cytokine-induced killer cells
• gastric cancer
• red blood cells

• Chemotherapy
• Improving cytokine-induced killer cells (iCIKs)
• PD-1
• PD-L1
• Tongue squamous cell carcinoma (TSCC)

• Antibodies
• antimicrobial peptides
• cell therapy
• cytokines
• gene therapy
• pulmonary tuberculosis

Purpose of our study was to explore a new immunotherapy for high grade soft tissue sarcomas (STS) based on cytokine-induced killer cells (CIK) redirected with a chimeric antigen receptor (CAR) against the tumor-promoting antigen CD44v6. We aimed at generating bipotential killers, combining the CAR specificity with the intrinsic tumor-killing ability of CIK cells (CAR⁺.CIK). We set a patient-derived experimental platform. CAR⁺.CIK were generated by transduction of CIK precursors with a lentiviral vector encoding for anti-CD44v6-CAR. CAR⁺.CIK were characterized and assessed in vitro against multiple histotypes of patient-derived STS. The anti-sarcoma activity of CAR⁺.CIK was confirmed in a STS xenograft model. CD44v6 was expressed by 40% (11/27) of patient-derived STS. CAR⁺.CIK were efficiently expanded from patients (n = 12) and killed multiple histotypes of STS (including autologous targets, n = 4). The killing activity was significantly higher compared with unmodified CIK, especially at low effector/target (E/T) ratios: 98% vs 82% (E/T = 10:1) and 68% vs 26% (1:4), (p<0.0001). Specificity of tumor killing was confirmed by blocking with anti-CD44v6 antibody. CAR⁺.CIK produced higher amounts of IL6 and IFN-γ compared to control CIK. CAR⁺.CIK were highly active in mice bearing subcutaneous STS xenografts, with significant delay of tumor growth (p<0.0001) without toxicities.

We report first evidence of CAR⁺.CIK's activity against high grade STS and propose CD44v6 as an innovative target in this setting. CIK are a valuable platform for the translation of CAR-based strategies to challenging field of solid tumors. Our findings support the exploration of CAR⁺.CIK in clinical trials against high grade STS.

• CAR
• CD44v6
• CIK
• adoptive immunotherapy
• soft tissue sarcoma

• CIK
• GvHD
• NK

• Animals
• Cytokine-Induced Killer Cells/cytology
• Cytokine-Induced Killer Cells/immunology
• Humans
• Immunotherapy/methods
• Neoplasms/immunology
• Neoplasms/therapy

The aim of this study was to systematically evaluate the efficacy and safety of the combination of dendritic cells and cytokine-induced killer cells (DC–CIK) adjuvant immunotherapy and chemotherapy in the treatment of multiple myeloma (MM).

Clinical trials were gathered by searching Web of Science, PubMed, Embase, Cochrane Library, Wanfang, and CNKI database. Outcome measurements including therapeutic efficacy, prognosis, immune function, and adverse events were extracted and evaluated.

A total of 12 trials including 594 MM patients were involved in this study for statistical analysis. Results indicated that compared to chemotherapy alone, the combination of DC–CIK immunotherapy with chemotherapy significantly improved patients’ overall response rate (ORR, odds ratio [OR] =2.77, 95% confidence interval [CI] =1.88–4.10, P<0.00001), disease control rate (DCR, OR =2.90, CI =1.72–4.90, P<0.0001), and life quality (P<0.00001). The combined therapy showed advantages over chemotherapy alone in prognostic indicators including percentage of tumor cells (P=0.04), serum levels of β2-microglobin (P<0.0001), M protein (P<0.00001), and creatinine (P<0.0001), and 24 h urine light chains (P<0.00001). After combined treatment, CD4⁺ lymphocyte subsets’ percentages, CD4⁺/CD8⁺ ratio, and cytokines levels of AgNOR, IFN-γ, IL-2, and IL-12 were significantly increased (P<0.05), whereas CD8⁺ and CD4⁺CD25⁺ percentages and IL-4, IL-6, IL-10, and TGF-β levels were obviously decreased (P<0.01), indicating a recovered immune condition.

Adjuvant DC–CIK immunotherapy enhances the efficacy of chemotherapy for MM and improves prognosis probably by reconstructing immune function.

• adjuvant immu-notherapy
• cytokine-induced killer cells
• dendritic cells
• meta-analysis
• multiple myeloma

• Animals
• Asthma/complications
• Asthma/immunology
• Asthma/metabolism
• Asthma/therapy
• Cell- and Tissue-Based Therapy/methods
• Cytokine-Induced Killer Cells/cytology
• Cytokines/biosynthesis
• Eosinophils/immunology
• Goblet Cells/pathology
• Hyperplasia
• Hypersensitivity/complications
• Killer Cells, Natural/cytology
• Killer Cells, Natural/immunology
• Male
• Mice
• Th1 Cells/cytology
• Th1 Cells/immunology

• Thailand Research Fund
• Siriraj Foundation

• blood cancer
• immunosurveillance
• immunotherapy
• invariant natural killer T
• natural killer T cells
• tumor immune evasion

• T-cell subsets
• advanced cancer
• cytokine-induced killer cells
• dendritic cells
• immunotherapy
• overall survival

• cancer therapy
• clinical trials
• cytokine-induced killer cells
• immunotherapy
• pharmacological tools

• adoptive cells therapy
• cytokine induced killer cell
• immunotherapy
• liver cancer
• meta-analysis

• Asia
• Carcinoma, Hepatocellular/mortality
• Carcinoma, Hepatocellular/pathology
• Carcinoma, Hepatocellular/therapy
• Clinical Trials as Topic
• Cytokine-Induced Killer Cells/immunology
• Cytokine-Induced Killer Cells/transplantation
• Humans
• Immunotherapy, Adoptive/adverse effects
• Immunotherapy, Adoptive/methods
• Liver Neoplasms/mortality
• Liver Neoplasms/pathology
• Liver Neoplasms/therapy
• Lymphocyte Subsets/immunology
• Lymphocyte Subsets/metabolism
• Publication Bias
• Safety Management
• Transplantation, Autologous
• Treatment Outcome

• Hodgkin lymphoma
• PD-1
• brentuximab vedotin
• clinical trials
• immunotherapy

The impact of epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors (TKIs) on the human immune system remains undefined. This study illustrates the immunomodulatory effect of gefitinib in patients with advanced non-small cell lung cancer (NSCLC) and its relevant prognostic significance.

Peripheral blood samples were collected from 54 patients at baseline and after 4 weeks of gefitinib treatment. Circulating lymphocyte populations and cytokine levels were measured. Pilot investigation of the impact of gefitinib on programmed cell death ligand-1 (PD-L1) expression was conducted by immunohistochemistry (IHC).

A significant increase of peripheral natural killer cells and interferon-gamma (INF-γ) after 4 weeks of gefitinib treatment (P=0.005 and 0.02, respectively). In addition, circulating interleukin (IL)-6 was significantly decreased, especially in patients sensitive to gefitinib (P<0.001). Higher levels of IL-6 at baseline independently correlated with poorer progression-free survival. Experiments with NSCLC specimens illustrated that PD-L1 expression were downregulated after 4 weeks of gefitinib treatment. In summary, it was found that gefitinib treatment can alter circulating cytokines and lymphocytes. Dynamic changes of circulating lymphocytes, cytokines, and even PD-L1 IHC expression around gefitinib treatment support the specific immunomodulatory effect of this agent for advanced NSCLC.

• PD-L1
• cytokine
• gefitinib
• lymphocyte
• non-small cell lung cancer

• Cytokine-induced killer
• DFS
• Dendritic cell
• Immunotherapy
• OS
• Stage IV breast cancer

• CIK
• cell therapy
• multi-drug resistant tuberculosis

The successful of transplantation is determined by the shared human leukocyte antigens (HLAs) and ABO blood group antigens between donor and recipient. In recent years, killer cell receptor [i.e., killer cell immunoglobulin-like receptor (KIR)] and major histocompatibility complex (MHC) class I chain-related gene molecule (i.e., MICA) were also reported as important determinants of transplant compatibility. At present, several different genotyping techniques (e.g., sequence specific primer and sequence based typing) can be used to characterize blood group, HLA, MICA and KIR and loci. These molecular techniques have several advantages because they do not depend on the availability of anti-sera, cellular expression and have greater specificity and accuracy compared with the antibody-antigen based typing. Nonetheless, these molecular techniques have limited capability to capture increasing number of markers which have been demonstrated to determine donor and recipient compatibility. It is now possible to genotype multiple markers and to the extent of a complete sequencing of the human genome using next generation sequencer (NGS). This high throughput genotyping platform has been tested for HLA, and it is expected that NGS will be used to simultaneously genotype a large number of clinically relevant transplantation genes in near future. This is not far from reality due to the bioinformatics support given by the immunogenetics community and the rigorous improvement in NGS methodology. In addition, new developments in immune tolerance based therapy, donor recruitment strategies and bioengineering are expected to provide significant advances in the field of transplantation medicine.

• Transplantation
• ABO blood group
• Human leukocyte antigen
• MICA
• Killer cell immunoglobulin-like receptor
• Graft rejection
• Graft vs host disease

• CD3/CD28 beads co-stimulated T cells
• Cytokine-induce killer cells
• Cytotoxicity
• Memory T cell subsets

• cytokine-induced killer cells
• dendritic cells
• gastric cancer
• immunotherapy
• meta-analysis

• CIK cell
• Chemotherapy
• Clinical trial
• Gastrointestinal cancer

• Adult
• Aged
• Antineoplastic Agents/therapeutic use
• Biomarkers, Tumor
• Cell Transplantation
• Combined Modality Therapy
• Cytokine-Induced Killer Cells/immunology
• Female
• Gastrointestinal Neoplasms/drug therapy
• Gastrointestinal Neoplasms/therapy
• Humans
• Male
• Middle Aged

• CD155
• CIK cells
• DNAM-1
• Immunotherapy
• TIGIT

• Antigens, Differentiation, T-Lymphocyte/physiology
• Cell Line, Tumor
• Cytokine-Induced Killer Cells/immunology
• Cytotoxicity, Immunologic
• Humans
• Receptors, Immunologic/physiology
• Receptors, Virus/physiology
• Signal Transduction/physiology

• POEMS syndrome
• clinical efficacy and safety
• cyclophosphamide
• cytokine-induced killer (CIK) cell
• lymphocyte
• vascular endothelial growth factor (VEGF)

Natural killer T (NKT) cells are innate-like lymphocytes that were first described in the late 1980s. Since their initial description, numerous studies have collectively shed light on their development and effector function. These studies have highlighted the unique requirements for the activation of these lymphocytes and the functional responses that distinguish these cells from other effector lymphocyte populations such as conventional T cells and NK cells. This body of literature suggests that NKT cells play diverse nonredundant roles in a number of disease processes, including the initiation and propagation of airway hyperreactivity, protection against a variety of pathogens, development of autoimmunity, and mediation of allograft responses. In this review, however, we focus on the role of a specific lineage of NKT cells in antitumor immunity. Specifically, we describe the development of invariant NKT (iNKT) cells and the factors that are critical for their acquisition of effector function. Next, we delineate the mechanisms by which iNKT cells influence and modulate the activity of other immune cells to directly or indirectly affect tumor growth. Finally, we review the successes and failures of clinical trials employing iNKT cell-based immunotherapies and explore the future prospects for the use of such strategies.

• Adult
• Aged
• Aged, 80 and over
• Cytokine-Induced Killer Cells
• Female
• Humans
• Immunotherapy/adverse effects
• Immunotherapy/methods
• International Cooperation
• Male
• Middle Aged
• Neoplasms/immunology
• Neoplasms/therapy
• Quality of Life
• Registries
• Treatment Outcome