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Special Issue "Cancer Immunotherapy Using Natural Killer Cells: Successes and Challenges of the Field"
A special issue of Cancers (ISSN 2072-6694).
Deadline for manuscript submissions: 15 January 2020.
Interests: natural killer cells; differentiation; cancer stem cells/poorly differentiated tumors
Renewed interest in adoptive NK cell therapy has generated quite a lot of enthusiasm among NK cell biologists in recent years. The demonstration of the ability of NK cells to target cancer stem cells and poorly differentiated tumors that lack or express very low levels of MHC class I has afforded these cells a very unique and indispensable role in cancer immunotherapy. It is also known that cancer patients have significantly suppressed NK cell numbers and function, and indeed, inactivation of NK function has been shown to occur at the pre-neoplastic stages of tumorigenesis, making these cells as one of the most important immune effectors responsible for the curtailment or inhibition of cancer.
However, limitation in the expansion of NK cells to sufficient numbers for clinical use, inability to obtain functional NK cells from different cellular sources, and lack of adequate understanding of the immunobiology of these cells have traditionally hampered the progress in the field of NK cell Immunotherapy. NK and T cells have to operate within a very complex and immunosuppressive tumor microenvironment. To this end, tumor infiltrating fat cells and fibroblasts which constitute important components of stromal cells in addition to MDSCs and Tregs may not only shape the numbers and function of NK cells but also other immune effectors such as CD8+ T cells. Indeed, recent work from our laboratory indicates that obesity in combination with genetic alterations in the pancreas is a driving force for NK cell immunosuppression at the pre-neoplastic stage of tumorigenesis.
Therefore, strategies should be designed to allow maintenance of good NK expansion and function in cancer patients, since NK cells are known to limit the expansion of tumor-associated macrophages (TAMs), Tregs, and MDSCs and result in the removal of CSCs/undifferentiated tumors, all of which are the hallmarks of aggressive tumors. Large numbers of functionally competent NK cells can be combined with other immunotherapeutic strategies, such as oncolytic viruses, ADCC-inducing antibodies, check point inhibitors, CAR-T, CAR-NK, TIL, and chemotherapeutic and radiotherapeutic strategies for the ultimate goal of tumor eradication.
This collection of reviews and original articles presented in this volume highlights the significant advances made in the field of NK cells and potential new directions which should help to advance the field and bring us to the finish line. After all, we should not forget that the beneficiaries are all those who have valiantly fought against cancer and are looking up to the scientific community for treatments that are not only effective in curing their cancer but also allowing them to enjoy a good quality of life.
Prof. Dr. Anahid Jewett
Manuscript Submission Information
Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.
Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access monthly journal published by MDPI.
Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.
- NK cells
- Cancer stem cells
- NK immunotherapy
The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.
Killer signaling of natural tumor recognition
Lizeth G. Meza Guzman1,2 and Sandra E. Nicholson1,2
1 The Walter and Eliza Hall Institute of Medical Research. Parkville, Victoria, Australia,
2 Department of Medical Biology, The University of Melbourne, Victoria, Australia
Natural killer (NK) cells play a pivotal role in cancer-immunotherapy due to their innate ability to target and kill tumorigenic cells. NK cells engage and kill tumour cells by expressing a myriad of activating and inhibitory receptors. Cell-to-cell engagement results in either self-tolerance or a cytotoxic response, which is regulated through a fine balance of the signalling cascades downstream of the activating and inhibitory receptors. Although a cytotoxic response is favourable when engaging tumour cells, tumour cells can modulate the surface expression of receptor ligands in order to escape the immune system. Additionally, harsh conditions in the tumour microenvironment (TME) tilt the scales towards a suppressed cytotoxic NK response. In order to fully harness the killing power of NK cells for clinical benefit, we need to understand what defines the threshold for activation and what is required to break tolerance within the TME. This review will focus on the intracellular signalling pathways activated or suppressed in NK cells within the TME and the roles the signalling intermediates play during an NK cytotoxic response.
Ovarian clear cell carcinoma is defectively recognized by autologous NK cells
Silvia Parolini, Giovanna Tabellini
Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy
In the present study, we report natural killer (NK) cell analysis derived from patients affected by rare ovarian cancer histotype of clear cell carcinoma (OCCC). We analyzed the phenoype of NK cells derived from peripheral bloods (PB) and peritoneal fluids (PF) and valuated on the first cytotoxic interaction between NK cells and autologous primary tumor cells derived from patients.We performed multiparametric cytofluorimetric analysis of NK cells and autologous tumor cells derived from six patients. We valuated cytotoxic capability, by degranulation assay, of patient NK cells against autologous clear cell carcinoma cells. We provide evidence of altered degranulation ability of NK cells derived from peritoneal fluid of patients /versus /autologous tumor cells. Moreover we also analyzed tumor cell ligands recognized by NK cell activating receptors and we show that patient NK cells were not able to recognize autologous tumor cells. So we think that this severe defect of lysis could be due to defective expression of NK cell receptor ligands stimulating various activating receptors. In the present study, for the first time, the phenotypic and functional properties of tumor associated NK cells derived from PF of six patients with advanced stage of OCCC are analyzed. These described altered interaction between NK cells and ATC lines begin to shed light on this particularly aggressive mechanisms of this histopyte tumor and will be fundamental expand the cases for more effective therapies.