Natural Killer Cells as a Double-edged Sword in Cancer Immunotherapy: A Comprehensive Review from Cytokine Therapy to Adoptive Cell Immunotherapy

Publication date: Available online 15 February 2020Source: Pharmacological ResearchAuthor(s): Yuanlin Wu, Jing Li, Parham Jabbarzadeh Kaboli, Jing Shen, Xu Wu, Yueshui Zhao, Huijiao Ji, Fukuan Du, Yejiang Zhou, Yongzhou Wang, Hanyu Zhang, Jianhua Yin, Qinglian Wen, Chi Hin Cho, Mingxing Li, Zhangang XiaoAbstractNatural killer (NK) cells are immune cells which are able to kill tumor and virus-infected cells and play an important role in both innate immunity and acquired immunity. Tumor immunotherapy is an emerging model of tumor treatment in the clinic. It is a re-emerging type of anticancer immunotherapy with the purpose of killing tumor cells by modulating the body’s immune function and enhancing the antitumor immunity in tumor microenvironment. At present, many immune cells including lymphokine-activated killer cells, natural killer cells, cytokine-induced killer cells, and dendritic cells are involved in tumor immunotherapy studies. NK cells, which lyse tumor cells without prior stimulation, has become a research hotspot in cancer immunotherapy for clinical application. In this article, we discussed the surface receptors of NK cells and the anticancer function of NK cells. We also reviewed the biological characteristics and the current research status of NK cells, their clinical application in cancer immunotherapy and its future perspectives.Graphical Abstract
Source: Pharmacological Research - Category: Drugs & Pharmacology Source Type: research

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CONCLUSION: Although tumor burden has been considered a mediator of efficacy of earlier immunotherapies, in advanced lung cancer it does not appear to affect outcomes from immune checkpoint inhibitors. IMPLICATIONS FOR PRACTICE: Historically, tumor burden has been considered an impediment to the efficacy of various immunotherapies, including vaccines, cytokines, allogeneic stem cell transplant, and intravesical bacillus Calmette-Guérin. However, in the present study, no association was found between tumor burden and efficacy (response rate, progression-free survival, overall survival) of immune checkpoint inhib...
Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Oncologist Source Type: research
Abstract PURPOSE: To evaluate the safety and feasibility of pre-operative locoregional cytokine therapy (IRX-2 regimen) in early stage breast cancer, and to evaluate for intratumoral and peripheral immunomodulatory activity. EXPERIMENTAL DESIGN: Sixteen patients with stage I-III early stage breast cancer (any histology type) indicated for surgical lumpectomy or mastectomy were enrolled to receive pre-operative locoregional immunotherapy with the IRX-2 cytokine biologic (2mL subcutaneous x 10 days to peri-areolar skin). The regimen also included single-dose cyclophosphamide (300mg/m2) on day 1 to deplete T-reg...
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
Zaravinos Different immunotherapeutic approaches have proved to be of significant clinical value to many patients with different types of advanced cancer. However, we need more precise immunotherapies and predictive biomarkers to increase the successful response rates. The advent of next generation sequencing technologies and their applications in immuno-oncology has helped us tremendously towards this aim. We are now moving towards the realization of personalized medicine, thus, significantly increasing our expectations for a more successful management of the disease. Here, we discuss the current immunotherapeutic app...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
AbstractGiven its poor prognosis, glioblastoma represents an area of high unmet clinical need. Standard of care for the treatment of glioblastoma in the frontline setting is limited to surgical resection, radiation, and temozolomide, with the more recent addition of Tumor Treating Fields. Several agents, including bevacizumab, lomustine, and carmustine have been approved in the recurrent setting. To date, no therapies have demonstrated substantial survival benefit beyond standard of care. An expanding understanding of the role of the immune system in fighting cancer has led to the development and approval of various immuno...
Source: Targeted Oncology - Category: Cancer & Oncology Source Type: research
ConclusionIn this retrospective analysis, HD IL-2 therapy displayed durable antitumor activity in mM and mRCC patients who progressed following treatment with PD-1 and PD-L1 inhibition. The toxicities were generally manageable and consistent with expectations from HD IL-2 but physicians should watch for immune related toxicities such as pneumonitis. This analysis supports the development of randomized prospective trials to assess the proper sequencing and combination of immune checkpoint blockade and cytokine therapy.
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
AbstractPurpose of ReviewImmune checkpoint inhibitors (ICI) are only effective in a subset of patients. Here, we will review the rationale and data supporting the combination of PD-1 pathway inhibition with recombinant cytokines and neoantigen-based cancer vaccines that can potentially increase the number of patients who will benefit from immunotherapy.Recent FindingsThe safety and tolerability of new interleukin(IL)-2 formulations, IL-15 super agonist, and PEGylated IL-10 have been evaluated in early phase clinical trials with promising efficacy data, both as monotherapy and in combination with ICI. Larger studies focusin...
Source: Current Oncology Reports - Category: Cancer & Oncology Source Type: research
AbstractCancer immunotherapy has shown impressive clinical results in the last decade, improving both solid and hematologic cancer patients ’ overall survival. Nevertheless, most of the molecular aspects underlying the response to this approach are still under investigation. miRNAs in particular have been described as regulators of a plethora of different immunologic processes and thus have the potential to be key in the future develo pments of immunotherapy. In this review, we summarize and discuss the emerging role of miRNAs in the diagnosis and therapeutics of the four principal cancer immunotherapy approaches: im...
Source: Cancer and Metastasis Reviews - Category: Cancer & Oncology Source Type: research
Authors: Subramaniam DS, Liu SV, Giaccone G Abstract Our understanding of tumor immunology has exploded in the past 3 decades. The complex relationships between tumor cells, the tumor microenvironment and the immune system cells, especially the cytotoxic and helper T cells and the regulatory T cells are beginning to be elucidated. In this review, we will attempt to provide a brief primer of tumor immunology. Cytokine therapy has historically been the mainstay of immunotherapy in cancers such as melanoma and kidney cancer. We will review some of the advances made with cancer vaccines, with a focus on peptide vaccine...
Source: Discovery Medicine - Category: Research Tags: Discov Med Source Type: research
Authors: Iacovelli R, Albiges L, Escudier B Abstract INTRODUCTION: Since both cytotoxic and cytokine therapy were not able to improve the prognosis of advanced renal cell carcinoma (RCC), this tumor has been a good model for the development of new biological agents in the past decade. Five VEGF receptor (VEGFR) and two mammalian target of rapamycin (mTOR) inhibitors are currently available for treatment of this disease but several issues need to be resolved such as a better definition of prognosis, the overcome of resistance and the best therapy for less frequent histologies. AREAS COVERED: This review focuses ...
Source: Expert Opinion on Emerging Drugs - Category: Drugs & Pharmacology Tags: Expert Opin Emerg Drugs Source Type: research
Publication date: Available online 17 December 2015 Source:Cell Reports Author(s): Anna Johansson-Percival, Zhi-Jie Li, Devina D. Lakhiani, Bo He, Xiao Wang, Juliana Hamzah, Ruth Ganss Normalization of the tumor vasculature is an emerging concept shown to improve anti-cancer therapy. However, there are currently no clinical interventions that effect long-lasting normalization. Here, we have developed a strategy for normalization by specific intratumoral delivery of LIGHT/TNFSF14. Importantly, normalization occurs by induced expression of contractile markers in intratumoral pericytes, which in turn re-establis...
Source: Cell Reports - Category: Cytology Source Type: research
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