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Special Issue "Cancer Immunoediting and Beyond"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: 30 April 2020.

Special Issue Editors

Dr. Fabio Grizzi
Website
Guest Editor
1. Department of Immunology and Inflammation, Humanitas Clinical and Research Hospital, Via Manzoni 56 - Rozzano, 20089, Milan, Italy
2. Humanitas University, Via Rita Levi Montalcini, Pieve Emanuele, 20090, Milan, Italy
Interests: Immunity; Cancer; Immunotherapy; histology; image analysis; modelling; chaos theory; fractal geometry
Special Issues and Collections in MDPI journals
Prof. Elena Monica Borroni
Website
Guest Editor
Department of Medical Biotechnologies and Translational Medicine, University of Milan, Segrate (Milan), Italy
Interests: cancer; immunology; microenvironment; leukocytes; chemokine system; signaling

Special Issue Information

Dear Colleagues,

Human cancer is one of the most complex dynamic diseases. Despite rapid advances in the fields of molecular and cell biology, it is still widely debated as to how neoplastic cells progress through carcinogenesis and acquire their metastatic ability. Evidence has been accumulating since the middle of the last century, from animal models as well as from investigations in cancer patients, that the immune system can recognize and reject tumors. Tumor cells are constantly eliminated by the immune system, but some of them establish a long-term equilibrium phase leading to tumor “immunoediting” (i.e., the relationship between the tumor cells and the immune system, which mainly consists of three phases named elimination, equilibrium, and escape) and, eventually, “evasion”. It is known that during this dynamical process, tumor cells tend to acquire adjunctive mutations, leading to a greater number of new antigens with the potential to initiate an immune response. Although many tumors evoke an immune response, tumor clearance by the immune system does not occur due to a suppressive tumor microenvironment. Tumor immunology has, therefore, a growing need to comprehend the components of the immune system that are important for tumor immunosurveillance and tumor rejection to understand how, when, and why they fail in cases of clinical disease.

This Special Issue will contain a collection of manuscripts that describe investigations into the different stages of tumor “immunoediting”, covering a range of model systems and tumor types. The latest research articles and reviews that aim to clarify concepts, interpret experimental data, indicate specific experiments, and categorize a rich body of knowledge on the basis of the similarities and/or shared behaviors of very different tumors are welcome.

Prof. Fabio Grizzi
Prof. Elena Monica Borroni
Guest Editors

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • tumor immunoediting
  • tumor complexity
  • immunotherapy
  • immuno-oncology
  • cancer heterogeneity
  • chemokines
  • cytokines
  • immunosurveillance
  • microenvironment
  • stromal remodeling
  • innate immunity
  • adaptive immunity
  • modeling
  • bioinformatics

Published Papers (5 papers)

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Research

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Open AccessArticle
Correlative Monitoring of Immune Activation and Tissue Damage in Malignant Melanoma—An Algorithm for Identification of Tolerance Breakage During Immune Checkpoint Inhibitor Therapy of Cancer
Int. J. Mol. Sci. 2020, 21(6), 2020; https://doi.org/10.3390/ijms21062020 - 16 Mar 2020
Abstract
We describe an innovative approach for identification of tolerance breakage during immune checkpoint inhibitor therapy in malignant melanoma. Checkpoint inhibitor therapy enhances the immunologic clearance of cancer by suppressing pathways which induce immune suppression and tolerance. We posit that by analyzing temporal correlations [...] Read more.
We describe an innovative approach for identification of tolerance breakage during immune checkpoint inhibitor therapy in malignant melanoma. Checkpoint inhibitor therapy enhances the immunologic clearance of cancer by suppressing pathways which induce immune suppression and tolerance. We posit that by analyzing temporal correlations of key markers of immune activation and tissue damage it would be possible to detect the onset of anticancer immune reaction as well as of immunologic adverse effects which might become crucial for optimization as well as safety of immune checkpoint inhibitor treatment. We analyzed time courses of routine laboratory values of serum tumor markers as well as of markers of immune activation in 17 patients with metastasized malignant melanoma receiving checkpoint inhibition and weekly laboratory controls. A parallel serum level increase of interleukin-6 and the tumor marker S100B could be identified in 13 patients, suggesting that the onset of tolerance breakage under checkpoint inhibition may be identified and measured. Immune-related adverse events in the patients were also accompanied by a peak of IL-6. In six patients, the onset of a putative anticancer immune reaction and the beginning of immunologic adverse events occurred in the same treatment cycle; in six patients the immunologic adverse reactions took place in separate cycles. Full article
(This article belongs to the Special Issue Cancer Immunoediting and Beyond)
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Open AccessArticle
DEK Is a Potential Biomarker Associated with Malignant Phenotype in Gastric Cancer Tissues and Plasma
Int. J. Mol. Sci. 2019, 20(22), 5689; https://doi.org/10.3390/ijms20225689 - 13 Nov 2019
Abstract
Gastric cancer (GC) is the second most widespread cause of cancer-related mortality worldwide. The discovery of novel biomarkers of oncoproteins can facilitate the development of therapeutic strategies for GC treatment. In this study, we identified novel biomarkers by integrating isobaric tags for relative [...] Read more.
Gastric cancer (GC) is the second most widespread cause of cancer-related mortality worldwide. The discovery of novel biomarkers of oncoproteins can facilitate the development of therapeutic strategies for GC treatment. In this study, we identified novel biomarkers by integrating isobaric tags for relative and absolute quantitation (iTRAQ), a human plasma proteome database, and public Oncomine datasets to search for aberrantly expressed oncogene-associated proteins in GC tissues and plasma. One of the most significantly upregulated biomarkers, DEK, was selected and its expression validated. Our immunohistochemistry (IHC) (n = 92) and quantitative real-time polymerase chain reaction (qRT-PCR) (n = 72) analyses disclosed a marked increase in DEK expression in tumor tissue, compared with paired nontumor mucosa. Importantly, significantly higher preoperative plasma DEK levels were detected in GC patients than in healthy controls via enzyme-linked immunosorbent assay (ELISA). In clinicopathological analysis, higher expression of DEK in both tissue and plasma was significantly associated with advanced stage and poorer survival outcomes of GC patients. Data from receiver operating characteristic (ROC) curve analysis disclosed a better diagnostic accuracy of plasma DEK than carcinoembryonic antigen (CEA), carbohydrate antigen 19.9 (CA 19.9), and C-reactive protein (CRP), highlighting its potential as an effective plasma biomarker for GC. Plasma DEK is also more sensitive in tumor detection than the other three biomarkers. Knockdown of DEK resulted in inhibition of GC cell migration via a mechanism involving modulation of matrix metalloproteinase MMP-2/MMP-9 level and vice versa. Our results collectively support plasma DEK as a useful biomarker for making diagnosis and prognosis of GC patients. Full article
(This article belongs to the Special Issue Cancer Immunoediting and Beyond)
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Open AccessArticle
Identification of 15 T Cell Restricted Genes Evaluates T Cell Infiltration of Human Healthy Tissues and Cancers and Shows Prognostic and Predictive Potential
Int. J. Mol. Sci. 2019, 20(20), 5242; https://doi.org/10.3390/ijms20205242 - 22 Oct 2019
Abstract
T cell gene signatures are used to evaluate T cell infiltration of non-lymphoid tissues and cancers in both experimental and clinical settings. However, some genes included in the available T cell signatures are not T cell-restricted. Herein, we propose a new human T [...] Read more.
T cell gene signatures are used to evaluate T cell infiltration of non-lymphoid tissues and cancers in both experimental and clinical settings. However, some genes included in the available T cell signatures are not T cell-restricted. Herein, we propose a new human T cell signature that has been developed via a six-step procedure and comprises 15 T cell restricted genes. We demonstrate the new T cell signature, named signature-H, that differs from other gene signatures since it shows higher sensitivity and better predictivity in the evaluation of T cell infiltration in healthy tissues as well as 32 cancers. Further, results from signature-H are highly concordant with the immunohistochemistry methods currently used for assessing the prognosis of neuroblastoma, as demonstrated by the Kaplan–Meier curves of patients ranked by tumor T cell infiltration. Moreover, T cell infiltration levels calculated using signature-H correlate with the risk groups determined by the staging of the neuroblastoma. Finally, multiparametric analysis of tumor-infiltrating T cells based on signature-H let us favorably predict the response of melanoma to the anti-PD-1 antibody nivolumab. These findings suggest that signature-H evaluates T cell infiltration levels of tissues and may be used as a prognostic tool in the precision medicine perspective after appropriate clinical validation. Full article
(This article belongs to the Special Issue Cancer Immunoediting and Beyond)
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Review

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Open AccessReview
Immunosurveillance and Immunoediting of Lung Cancer: Current Perspectives and Challenges
Int. J. Mol. Sci. 2020, 21(2), 597; https://doi.org/10.3390/ijms21020597 - 17 Jan 2020
Abstract
The immune system plays a dual role in tumor evolution—it can identify and control nascent tumor cells in a process called immunosurveillance and can promote tumor progression through immunosuppression via various mechanisms. Thus, bilateral host-protective and tumor-promoting actions of immunity are integrated as [...] Read more.
The immune system plays a dual role in tumor evolution—it can identify and control nascent tumor cells in a process called immunosurveillance and can promote tumor progression through immunosuppression via various mechanisms. Thus, bilateral host-protective and tumor-promoting actions of immunity are integrated as cancer immunoediting. In this decade, immune checkpoint inhibitors, specifically programmed cell death 1 (PD-1) pathway inhibitors, have changed the treatment paradigm of advanced non-small cell lung cancer (NSCLC). These agents are approved for the treatment of patients with NSCLC and demonstrate impressive clinical activity and durable responses in some patients. However, for many NSCLC patients, the efficacy of immune checkpoint inhibitors is limited. To optimize the full utility of the immune system for eradicating cancer, a broader understanding of cancer immunosurveillance and immunoediting is essential. In this review, we discuss the fundamental knowledge of the phenomena and provide an overview of the next-generation immunotherapies in the pipeline. Full article
(This article belongs to the Special Issue Cancer Immunoediting and Beyond)
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Open AccessReview
Targeting Immune-Related Biological Processes in Solid Tumors: We do Need Biomarkers
Int. J. Mol. Sci. 2019, 20(21), 5452; https://doi.org/10.3390/ijms20215452 - 01 Nov 2019
Cited by 1
Abstract
Immunotherapy has become the standard-of-care in many solid tumors. Despite the significant recent achievements in the diagnosis and treatment of cancer, several issues related to patients’ selection for immunotherapy remain unsolved. Multiple lines of evidence suggest that, in this setting, the vision of [...] Read more.
Immunotherapy has become the standard-of-care in many solid tumors. Despite the significant recent achievements in the diagnosis and treatment of cancer, several issues related to patients’ selection for immunotherapy remain unsolved. Multiple lines of evidence suggest that, in this setting, the vision of a single biomarker is somewhat naïve and imprecise, given that immunotherapy does not follow the rules that we have experienced in the past for targeted therapies. On the other hand, additional immune-related biomarkers that are reliable in real-life clinical practice remain to be identified. Recently, the immune-checkpoint blockade has been approved in the US irrespective of the tumor site of origin. Further histology-agnostic approvals, coupled with with tumor-specific companion diagnostics and guidelines, are expected in this field. In addition, immune-related biomarkers can also have a significant prognostic value. In this review, we provide an overview of the role of these biomarkers and their characterization in the management of lung cancer, melanoma, colorectal cancer, gastric cancer, head and neck cancer, renal cell carcinoma, urothelial cancers, and breast cancer. Full article
(This article belongs to the Special Issue Cancer Immunoediting and Beyond)
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Planned Papers

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.

Title: Correlative Monitoring of Immune-Activation and Tissue-Damage–A Universal Algorithm for Identification of Tolerance Breakage During Checkpoint-Inhibitor Therapy of Cancer

Author: Albert Rübben (University Hospital of the RWTH Aachen)

Absract: Checkpoint-inhibitor therapy of cancer enhances the immunologic clearance of cancer cells by suppressing pathways which induce immune suppression and tolerance. By analyzing temporal correlation of key markers of immune activation and tissue damage, it is possible to detect the onset of anti-cancer immune reaction as well as the onset of immunologic side effects which is crucial for optimization as well as safety of immune checkpoint-inhibitor treatment. The algorithm and preliminary data of melanoma patients will be presented.

Title: Immunosurveillance and Immunoediting of Lung Cancer: Current Perspectives and Challenges

Author: Taichiro Goto (Yamanashi Central Hospital)

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