Novel TLR7 agonist stimulates activity of CIK/NK immunological effector cells to enhance antitumor cytotoxicity

Gao, Dong; Cai, Yongguang; Chen, Yanyuan; Li, Wang; Wei, Chih‐Chang; Luo, Xi; Wang, Yuhuan

doi:10.3892/ol.2018.7954

Cited by 4 publications

(4 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The two NRPs were tested: NRP1 and NRP2 and flow cytometry and RT-qPCR were performed. As a positive control, the cell lines A549 and U251-MG were used, since they have been already proven to express NRP1 and/or NRP2 (16,17).…”

Section: Discussionmentioning

confidence: 99%

Presence of the Transmembrane Protein Neuropilin in Cytokine-induced Killer Cells

et al. 2020

View full text Add to dashboard Cite

Background/Aim: Cytokine-induced killer (CIK) cells are a heterogenous population of immune cells showing promising applications in immunotherapeutic cancer treatment. Neuropilin (NRP) proteins have been proven to play an important role in cancer development and prognosis. In this study, CIK cells were tested for expression of NRPs, transmembrane proteins playing a role in the proliferation and survival of cancer cells. Materials and Methods: CIK cells were analyzed at different time points via flow cytometry and quantitative real-time polymerase chain reaction for neuropilin expression. Results: Phenotyping results showed CIK cells having developed properly, and low levels of NRP2 were detected. On the other hand, no NRP1 expression was found. Two cancer cell lines were tested by flow cytometry: A549 cells expressed NRP1 and NRP2; U251-MG cells expressed high amounts of NRP2. CIK cell showed low levels of NRP2 expression on day 14. Conclusion: The presence of NRP2, but not NRP1, was shown for CIK cells. Recognizing NRP2 in CIK cells might help to improve CIK cell cytotoxicity.Neuropilins (NRPs) are non-tyrosine kinase glycoproteins expressed on the surface of cells of all vertebrate animals. There are two main molecules, NRP1 and NRP2 (located on different genes), which act as co-receptors for certain molecules. NRPs bind vascular endothelial growth factors (VEGFs), class III semaphorins, transforming growth factor beta, other growth factors and many more molecules (1).Depending on what they bind, different pathways/signals are either induced or up-regulated. Regarding their effects on tumor cells, interactions of class III semaphorins and NRPs/plexins on cancer cells have been reported to induce inhibition of proliferation, migration, angiogenesis and immune responses (2). On the other hand, when VEGF molecules interact with NRPs, cell survival, proliferation, migration, angiogenesis and metastasis are induced (1).Previous studies have focused on the role of NRPs on cancer cells, finding a pattern that highlights a positive correlation between the expression of NRPs in tumor cells and the malignancy of the same (1-3). Lal Goel et al. found that NRP-2 is associated with high-grade prostate cancer (4), it was also found to be a prognostic marker for survival in prostate cancer (5). Another study showed how the silencing of NRP1 in nonsmall cell lung carcinomas reduced proliferation and increased radiosensitivity of the tumor cells both in vitro and in vivo (6). Therefore, NRPs are becoming a protein of increasing importance in regard to oncology research.Cytokine-induced killer cells (CIK) are expanded ex-vivo from peripheral blood mononuclear cells (PBMCs) of a patient's blood. They were firstly characterized by Schmidt-Wolf et al. in 1991 (7) and have been the focus of various prospective oncology therapies since (8). They have certain characteristic features which make them great candidates for adoptive immunotherapy: They are able to lyse tumor cells independently of the major histocompatibility complex, the...

show abstract

Section: Discussionmentioning

confidence: 99%

Presence of the Transmembrane Protein Neuropilin in Cytokine-induced Killer Cells

et al. 2020

View full text Add to dashboard Cite

show abstract

“…The proportion of CIK cells are a group of immune effector cells characterized by the cell surface marker CD3 − CD56 + and the proportion of NK cells are a type of lymphocytes, which are distinguished by the cell surface marker CD3-CD56+ (39). Both CIK and NK cells play critical role in immune anti-tumor effect (40). The ratio of CD3+CD56+ CIK, CD3-CD56+ NK or total CD3+/-CD56+ CIK/NK cells accounts for of total mononuclear cells, which was calculated by the following formula: Ratio of CIK cells (%)=number of cells (CD3 + CD56 + )/number of cells (all MNCs); ratio of NK cells (%)=number of cells (CD3 − CD56 + )/number of cells (all MNCs); ratio of total CIK/NK cells (%)=number of cells (CD3 +/− CD56 + )/number of cells (all MNCs).…”

Section: Methodsmentioning

confidence: 99%

Cytokine‑induced killer cells/natural killer cells combined with anti‑GD2 monoclonal antibody increase cell death rate in neuroblastoma SK‑N‑SH cells

Zhang

Xiong

et al. 2019

Oncol Lett

View full text Add to dashboard Cite

show abstract

“…151 Using toll-like receptor 7/8 agonist in combination with CIK cells improve approximately 21% to 25% of their cytotoxic activity against chronic myelogenous leukemia K562 cell line. 152…”

Section: Cik Cell Cytotoxicitymentioning

confidence: 99%

Promising immunotherapy: Highlighting cytokine‐induced killer cells

Shirjang

Alizadeh

Mansoori

et al. 2018

J of Cellular Biochemistry

View full text Add to dashboard Cite

For many years, cancer therapy has appeared to be a challenging issue for researchers and physicians. By the introduction of novel methods in immunotherapy, the prospect of cancer therapy even more explained than before. Cytokine-induced killer (CIK) cell-based immunotherapy demonstrated to have potentiality in improving clinical outcomes and relieving major side effects of standard treatment options. In addition, given the distinctive features such as high safety, low toxicity effects on healthy cells, numerous clinical trials conducted on CIK cells. Due to the shortcomings that observed in CIK cell immunotherapy alone, arising a tendency to make modifications (combined modality therapy or combination therapy) including the addition of various types of cytokines, genetic engineering, combination with immune checkpoints, and so on. In this review, we have tried to bring forth the latest immunotherapy methods and their overview. We have discussed the combination therapies with CIK cells and the conducted clinical trials. This helps the future studies to use integrated therapies with CIK cells as a promising treatment of many types of cancers. K E Y W O R D Scancer, combined modality therapy, cytokine-induced killer cells, immunotherapy

show abstract

Novel TLR7 agonist stimulates activity of CIK/NK immunological effector cells to enhance antitumor cytotoxicity

Cited by 4 publications

References 25 publications

Presence of the Transmembrane Protein Neuropilin in Cytokine-induced Killer Cells

Presence of the Transmembrane Protein Neuropilin in Cytokine-induced Killer Cells

Cytokine‑induced killer cells/natural killer cells combined with anti‑GD2 monoclonal antibody increase cell death rate in neuroblastoma SK‑N‑SH cells

Promising immunotherapy: Highlighting cytokine‐induced killer cells

Contact Info

Product

Resources

About