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Dear Colleagues,

This Special Issue is the continuation of our 2020 Special Issue “Natural Killer and NKT Cells 2020” and 2019 Special Issue “Natural Killer and NKT Cells”.

This Special Issue, “Cancer Immunotherapies & NK/CIK/CAR-T”, will cover a selection of recent research topics and current review articles in this field. Experimental papers, up-to-date review articles, and commentaries are all welcome.

Natural Killer (NK) and Natural Killer T (NKT) cells represent exceptional lymphocyte populations with major tumor-killing activity. NK cells possess activating as well as inhibitory receptors. Most NKT cells recognize the antigen-presenting molecule CD1d. NKT cells are classified into type 1 invariant, type 2 diverse, and NKT-like cells. NK and NKT cells have been shown to play an essential role in autoimmune diseases, as well as in cancer. NKT cells are present in peripheral blood mononuclear cells or cord blood in low numbers but can be expanded in vitro. Most clinical trials with NKT cells have been performed with Cytokine-Induced Killer (CIK) cells. CIK cells are licensed in various countries, e.g., in Germany.

Due to their easy availability and potent antitumor activity, NK and NKT cells have emerged as promising immunotherapeutic approaches in oncology and may become very important in the prognosis of cancer, e.g., in the context of checkpoint inhibition or CAR-T cells.

Prof. Dr. Ingo Schmidt-Wolf
Dr. Amit Sharma
Guest Editors

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Keywords

NK cells
NKT cells
cytokine-induced killer cells
transplantation
immunotherapy
cancer treatment
CAR-T cell
CAR-NK cell
CAR-NKT cell
checkpoint inhibition

Published Papers (2 papers)

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Research

17 pages, 2749 KiB

Open AccessArticle

Efficient Redirection of NK Cells by Genetic Modification with Chemokine Receptors CCR4 and CCR2B

by Frederik Fabian Feigl, Anika Stahringer, Matthias Peindl, Gudrun Dandekar, Ulrike Koehl, Stephan Fricke and Dominik Schmiedel

Int. J. Mol. Sci. 2023, 24(4), 3129; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24043129 - 04 Feb 2023

Cited by 5 | Viewed by 2834

Abstract

Natural killer (NK) cells are a subset of lymphocytes that offer great potential for cancer immunotherapy due to their natural anti-tumor activity and the possibility to safely transplant cells from healthy donors to patients in a clinical setting. However, the efficacy of cell-based immunotherapies using both T and NK cells is often limited by a poor infiltration of immune cells into solid tumors. Importantly, regulatory immune cell subsets are frequently recruited to tumor sites. In this study, we overexpressed two chemokine receptors, CCR4 and CCR2B, that are naturally found on T regulatory cells and tumor-resident monocytes, respectively, on NK cells. Using the NK cell line NK-92 as well as primary NK cells from peripheral blood, we show that genetically engineered NK cells can be efficiently redirected using chemokine receptors from different immune cell lineages and migrate towards chemokines such as CCL22 or CCL2, without impairing the natural effector functions. This approach has the potential to enhance the therapeutic effect of immunotherapies in solid tumors by directing genetically engineered donor NK cells to tumor sites. As a future therapeutic option, the natural anti-tumor activity of NK cells at the tumor sites can be increased by co-expression of chemokine receptors with chimeric antigen receptors (CAR) or T cell receptors (TCR) on NK cells can be performed in the future. Full article

(This article belongs to the Special Issue Cancer Immunotherapies and NK/CIK/CAR-T)

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12 pages, 3180 KiB

Open AccessArticle

A Low Dose of Pure Cannabidiol Is Sufficient to Stimulate the Cytotoxic Function of CIK Cells without Exerting the Downstream Mediators in Pancreatic Cancer Cells

by Francesca Garofano, Amit Sharma, Hinrich Abken, Maria A. Gonzalez-Carmona and Ingo G. H. Schmidt-Wolf

Int. J. Mol. Sci. 2022, 23(7), 3783; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23073783 - 29 Mar 2022

Cited by 7 | Viewed by 2512

Abstract

Despite numerous studies conducted over the past decade, the exact role of the cannabinoid system in cancer development remains unclear. Though research has focused on two cannabinoid receptors (CB1, CB2) activated by most cannabinoids, CB2 holds greater attention due to its expression in cells of the immune system. In particular, cytokine-induced killer cells (CIKs), which are pivotal cytotoxic immunological effector cells, express a high-level of CB2 receptors. Herein, we sought to investigate whether inducing CIK cells with cannabidiol can enhance their cytotoxicity and if there are any possible counter effects in its downstream cascade of phosphorylated p38 and CREB using a pancreatic ductal adenocarcinoma cell line (PANC-1). Our results showed that IL-2 modulates primarily the expression of the CB2 receptor on CIK cells used during ex vivo CIK expansion. The autophagosomal-associated scaffold protein p62 was found to co-localize with CB2 receptors in CIK cells and the PANC-1 cell line. CIK cells showed a low level of intracellular phospho-p38 and, when stimulated with cannabidiol (CBD), a donor specific variability in phospho-CREB. CBD significantly decreases the viability of PANC-1 cells presumably by increasing the cytotoxicity of CIK cells. Taken together, in our preclinical in vitro study, we propose that a low effective dose of CBD is sufficient to stimulate the cytotoxic function of CIK without exerting any associated mediator. Thus, the combinatorial approach of non-psychoactive CBD and CIK cells appears to be safe and can be considered for a clinical perspective in pancreatic cancer. Full article

(This article belongs to the Special Issue Cancer Immunotherapies and NK/CIK/CAR-T)

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