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Cancers
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Cytokines in Cancer Immunotherapy
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Cytokines in Cancer Immunotherapy

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Molecular Cancer Biology".

Deadline for manuscript submissions: closed (31 October 2021) | Viewed by 28580

Special Issue Editor

Prof. Dr. Leonidas C Platanias

E-Mail Website
Guest Editor
Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL 60611, USA
Interests: interferon; leukemia; immunotherapy; cytokines; signaling
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

This Special Issue will address the roles of key cytokines in the immune response to cancer and the generation of antitumor responses. The Issue will address the role of interferons in the immune response and their importance to cancer immunotherapy. It will discuss the mechanisms by which cytokines control the avidity and function of anti-tumor T cells and will provide an overview of the mechanisms of promotion of tumor development and the immune escape by interleukin 33 signaling. In addition, the role of the heterodimeric intereleukin-15 in tumor immunotherapy will be addressed. Finally, the roles of cytokines in the progression of brain metastases will be discussed.  Overall, the Issue will provide a comprehensive review of the roles of different cytokines in the immunotherapy of tumors.

Prof. Dr. Leonidas C Platanias
Guest Editor

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 submissions that pass pre-check are 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 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 semimonthly 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 2900 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.

Keywords

  • immunotherapy
  • interferons
  • cytokines
  • interleukin
  • T cells
  • immune escape

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Published Papers (5 papers)

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Review

25 pages, 1250 KiB  
Review
The Janus Face of IL-33 Signaling in Tumor Development and Immune Escape
by Mi-Ran Choi, Jeffrey A. Sosman and Bin Zhang
Cancers 2021, 13(13), 3281; https://doi.org/10.3390/cancers13133281 - 30 Jun 2021
Cited by 19 | Viewed by 4809
Abstract
Interleukin-33 (IL-33), a member of the IL-1 cytokine family, plays a critical role in maintaining tissue homeostasis as well as pathological conditions, such as allergy, infectious disease, and cancer, by promoting type 1 and 2 immune responses. Through its specific receptor ST2, IL-33 [...] Read more.
Interleukin-33 (IL-33), a member of the IL-1 cytokine family, plays a critical role in maintaining tissue homeostasis as well as pathological conditions, such as allergy, infectious disease, and cancer, by promoting type 1 and 2 immune responses. Through its specific receptor ST2, IL-33 exerts multifaceted functions through the activation of diverse intracellular signaling pathways. ST2 is expressed in different types of immune cells, including Th2 cells, Th1 cells, CD8+ T cells, regulatory T cells (Treg), cytotoxic NK cells, group 2 innate lymphoid cells (ILC2s), and myeloid cells. During cancer initiation and progression, the aberrant regulation of the IL-33/ST2 axis in the tumor microenvironment (TME) extrinsically and intrinsically mediates immune editing via modulation of both innate and adaptive immune cell components. The summarized results in this review suggest that IL-33 exerts dual-functioning, pro- as well as anti-tumorigenic effects depending on the tumor type, expression levels, cellular context, and cytokine milieu. A better understanding of the distinct roles of IL-33 in epithelial, stromal, and immune cell compartments will benefit the development of a targeting strategy for this IL-33/ST2 axis for cancer immunotherapy. Full article
(This article belongs to the Special Issue Cytokines in Cancer Immunotherapy)
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19 pages, 1183 KiB  
Review
Type I and II Interferons in the Anti-Tumor Immune Response
by Sarah E. Fenton, Diana Saleiro and Leonidas C. Platanias
Cancers 2021, 13(5), 1037; https://doi.org/10.3390/cancers13051037 - 2 Mar 2021
Cited by 58 | Viewed by 6512
Abstract
The interferons (IFNs) are essential components of the immune response against infections and malignancies. IFNs are potent promoters of the anti-tumor response, but there is also evidence that feedback mechanisms regulated by IFNs negatively control immune responses to avoid hyper-activation and limit inflammation. [...] Read more.
The interferons (IFNs) are essential components of the immune response against infections and malignancies. IFNs are potent promoters of the anti-tumor response, but there is also evidence that feedback mechanisms regulated by IFNs negatively control immune responses to avoid hyper-activation and limit inflammation. This balance of responses plays an important role in cancer surveillance, immunoediting and response to anticancer therapeutic approaches. Here we review the roles of both type I and type II IFNs on the control of the immune response against malignancies in the context of effects on both malignant cells and cells of the immune system in the tumor microenvironment. Full article
(This article belongs to the Special Issue Cytokines in Cancer Immunotherapy)
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Figure 1

20 pages, 1984 KiB  
Review
Heterodimeric IL-15 in Cancer Immunotherapy
by Cristina Bergamaschi, Vasiliki Stravokefalou, Dimitris Stellas, Sevasti Karaliota, Barbara K. Felber and George N. Pavlakis
Cancers 2021, 13(4), 837; https://doi.org/10.3390/cancers13040837 - 17 Feb 2021
Cited by 29 | Viewed by 6686
Abstract
Immunotherapy has emerged as a valuable strategy for the treatment of many cancer types. Interleukin-15 (IL-15) promotes the growth and function of cytotoxic CD8+ T and natural killer (NK) cells. It also enhances leukocyte trafficking and stimulates tumor-infiltrating lymphocytes expansion and activity. [...] Read more.
Immunotherapy has emerged as a valuable strategy for the treatment of many cancer types. Interleukin-15 (IL-15) promotes the growth and function of cytotoxic CD8+ T and natural killer (NK) cells. It also enhances leukocyte trafficking and stimulates tumor-infiltrating lymphocytes expansion and activity. Bioactive IL-15 is produced in the body as a heterodimeric cytokine, comprising the IL-15 and the so-called IL-15 receptor alpha chain that are together termed “heterodimeric IL-15” (hetIL-15). hetIL-15, closely resembling the natural form of the cytokine produced in vivo, and IL-15:IL-15Rα complex variants, such as hetIL-15Fc, N-803 and RLI, are the currently available IL-15 agents. These molecules have showed favorable pharmacokinetics and biological function in vivo in comparison to single-chain recombinant IL-15. Preclinical animal studies have supported their anti-tumor activity, suggesting IL-15 as a general method to convert “cold” tumors into “hot”, by promoting tumor lymphocyte infiltration. In clinical trials, IL-15-based therapies are overall well-tolerated and result in the expansion and activation of NK and memory CD8+ T cells. Combinations with other immunotherapies are being investigated to improve the anti-tumor efficacy of IL-15 agents in the clinic. Full article
(This article belongs to the Special Issue Cytokines in Cancer Immunotherapy)
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17 pages, 1149 KiB  
Review
A Palette of Cytokines to Measure Anti-Tumor Efficacy of T Cell-Based Therapeutics
by Prathyaya Ramesh, Rohan Shivde, Dinesh Jaishankar, Diana Saleiro and I. Caroline Le Poole
Cancers 2021, 13(4), 821; https://doi.org/10.3390/cancers13040821 - 16 Feb 2021
Cited by 25 | Viewed by 3924
Abstract
Cytokines are key molecules within the tumor microenvironment (TME) that can be used as biomarkers to predict the magnitude of anti-tumor immune responses. During immune monitoring, it has been customary to predict outcomes based on the abundance of a single cytokine, in particular [...] Read more.
Cytokines are key molecules within the tumor microenvironment (TME) that can be used as biomarkers to predict the magnitude of anti-tumor immune responses. During immune monitoring, it has been customary to predict outcomes based on the abundance of a single cytokine, in particular IFN-γ or TGF-β, as a readout of ongoing anti-cancer immunity. However, individual cytokines within the TME can exhibit dual opposing roles. For example, both IFN-γ and TGF-β have been associated with pro- and anti-tumor functions. Moreover, cytokines originating from different cellular sources influence the crosstalk between CD4+ and CD8+ T cells, while the array of cytokines expressed by T cells is also instrumental in defining the mechanisms of action and efficacy of treatments. Thus, it becomes increasingly clear that a reliable readout of ongoing immunity within the TME will have to include more than the measurement of a single cytokine. This review focuses on defining a panel of cytokines that could help to reliably predict and analyze the outcomes of T cell-based anti-tumor therapies. Full article
(This article belongs to the Special Issue Cytokines in Cancer Immunotherapy)
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17 pages, 715 KiB  
Review
The Network of Cytokines in Brain Metastases
by Jawad Fares, Alex Cordero, Deepak Kanojia and Maciej S. Lesniak
Cancers 2021, 13(1), 142; https://doi.org/10.3390/cancers13010142 - 5 Jan 2021
Cited by 25 | Viewed by 4975
Abstract
Brain metastases are the most common of all intracranial tumors and a major cause of death in patients with cancer. Cytokines, including chemokines, interferons, interleukins, lymphokines, and tumor necrosis factors are key regulators in the formation of brain metastases. They regulate the infiltration [...] Read more.
Brain metastases are the most common of all intracranial tumors and a major cause of death in patients with cancer. Cytokines, including chemokines, interferons, interleukins, lymphokines, and tumor necrosis factors are key regulators in the formation of brain metastases. They regulate the infiltration of different cellular subsets into the tumor microenvironment and affect the therapeutic outcomes in patients. Elucidating the cancer cell-cytokine interactions in the setting of brain metastases is crucial for the development of more accurate diagnostics and efficacious therapies. In this review, we focus on cytokines that are found in the tumor microenvironment of brain metastases and elaborate on their trends of expression, regulation, and roles in cellular recruitment and tumorigenesis. We also explore how cytokines can alter the anti-tumor response in the context of brain metastases and discuss ways through which cytokine networks can be manipulated for diagnosis and treatment. Full article
(This article belongs to the Special Issue Cytokines in Cancer Immunotherapy)
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