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Biomedicines
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Dissecting the Immunological Landscape of Human Malignancies
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Dissecting the Immunological Landscape of Human Malignancies

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Immunology and Immunotherapy".

Deadline for manuscript submissions: closed (31 December 2017) | Viewed by 62526

Special Issue Editor

Prof. Dr. Sergio Rutella

E-Mail Website
Guest Editor
College of Science and Technology, Clifton Campus, Nottingham Trent University, Nottingham NG11 8NS, UK
Interests: acute myeloid leukemia; immunotherapy; cancer genomics; cancer immunology; hematological malignancies

Special Issue Information

Dear Colleagues,

Tumours are organised tissues that are infiltrated with immune cell populations of both the lymphoid and myeloid lineage and possess both tumour-promoting and tumour-inhibiting properties. Pre-existing immunological features contribute to the ability of patients with cancer to respond to immunotherapy with immunomodulatory agents such as checkpoint inhibitors. This Special Issue will focus on novel tools, which are being developed to analyse the diversity of immune genes, proteins, cells and pathways in the tumour microenvironment. Powerful technologies, such as genome-wide association studies (GWAS), multiplexed immunohistochemistry, high-dimensional blood profiling of immune cells by flow cytometry and mass cytometry, are increasingly being integrated to assess immune competence and the likelihood of patients to respond to immunotherapy. A broader understanding of baseline immunity (the “immunoscore”), both in the periphery and in the tumour microenvironment, and of immune escape mechanisms is likely to expedite the identification of biomarkers that are predictive of clinical outcome and to foster the clinical implementation of a more refined and personalised approach to immune-based interventions.

Prof. Sergio Rutella
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 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. Biomedicines 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 2600 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

  • Biomarker
  • genomics
  • proteomics
  • cancer immunotherapy
  • immune profiling
  • immune checkpoints
  • tumour microenvironment

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Published Papers (7 papers)

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Review

24 pages, 2167 KiB  
Review
Dissecting the Immune Landscape of Acute Myeloid Leukemia
by Jan Davidson-Moncada, Elena Viboch, Sarah E. Church, Sarah E. Warren and Sergio Rutella
Biomedicines 2018, 6(4), 110; https://doi.org/10.3390/biomedicines6040110 - 25 Nov 2018
Cited by 26 | Viewed by 8644
Abstract
Acute myeloid leukemia (AML) is a molecularly heterogeneous hematological malignancy with variable response to treatment. Recurring cytogenetic abnormalities and molecular lesions identify AML patient subgroups with different survival probabilities; however, 50–70% of AML cases harbor either normal or risk-indeterminate karyotypes. The discovery of [...] Read more.
Acute myeloid leukemia (AML) is a molecularly heterogeneous hematological malignancy with variable response to treatment. Recurring cytogenetic abnormalities and molecular lesions identify AML patient subgroups with different survival probabilities; however, 50–70% of AML cases harbor either normal or risk-indeterminate karyotypes. The discovery of better biomarkers of clinical success and failure is therefore necessary to inform tailored therapeutic decisions. Harnessing the immune system against cancer with programmed death-1 (PD-1)-directed immune checkpoint blockade (ICB) and other immunotherapy agents is an effective therapeutic option for several advanced malignancies. However, durable responses have been observed in only a minority of patients, highlighting the need to gain insights into the molecular features that predict response and to also develop more effective and rational combination therapies that address mechanisms of immune evasion and resistance. We will review the state of knowledge of the immune landscape of AML and identify the broad opportunity to further explore this incompletely characterized space. Multiplexed, spatially-resolved immunohistochemistry, flow cytometry/mass cytometry, proteomic and transcriptomic approaches are advancing our understanding of the complexity of AML-immune interactions and are expected to support the design and expedite the delivery of personalized immunotherapy clinical trials. Full article
(This article belongs to the Special Issue Dissecting the Immunological Landscape of Human Malignancies)
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Figure 1

13 pages, 537 KiB  
Review
Immune Profiling of Cancer Patients Treated with Immunotherapy: Advances and Challenges
by Lorenzo Pilla and Cristina Maccalli
Biomedicines 2018, 6(3), 76; https://doi.org/10.3390/biomedicines6030076 - 2 Jul 2018
Cited by 12 | Viewed by 5829
Abstract
The recent advances in immunotherapy and the availability of novel drugs to target the tumor microenvironment have dramatically changed the paradigm of cancer treatment. Nevertheless, a significant proportion of cancer patients are unresponsive or develop resistance to these treatments. With the aim to [...] Read more.
The recent advances in immunotherapy and the availability of novel drugs to target the tumor microenvironment have dramatically changed the paradigm of cancer treatment. Nevertheless, a significant proportion of cancer patients are unresponsive or develop resistance to these treatments. With the aim to increase the clinical efficacy of immunotherapy, combinations of agents and standard therapies with complementary actions have been developed mostly on an empirical base, since their mechanisms of actions are not yet fully dissected. The characterization of immune responsiveness and its monitoring along with the treatment of cancer patients with immunotherapy can provide insights into the mechanisms of action of these therapeutic regimens and contribute to the optimization of patients’ stratification and of combination strategies and to the prediction of treatment-related toxicities. Thus far, none of the immunomonitoring strategies has been validated for routine clinical practice. Moreover, it is becoming clear that the genomic and molecular make-up of tumors and of the infiltrating immune system represent important determinants of the clinical responses to immunotherapy. This review provides an overview of different approaches for the immune profiling of cancer patients and discusses their advantages and limitations. Recent advances in genomic-based assays and in the identification of host genomic relationships with immune responses represent promising approaches to identify molecular determinants and biomarkers to improve the clinical efficacy of cancer immunotherapy. Full article
(This article belongs to the Special Issue Dissecting the Immunological Landscape of Human Malignancies)
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Graphical abstract

22 pages, 380 KiB  
Review
Current Strategies to Enhance Anti-Tumour Immunity
by Katherine W. Cook, Lindy G. Durrant and Victoria A. Brentville
Biomedicines 2018, 6(2), 37; https://doi.org/10.3390/biomedicines6020037 - 23 Mar 2018
Cited by 14 | Viewed by 6977
Abstract
The interaction of the immune system with cancer is complex, but new approaches are resulting in exciting therapeutic benefits. In order to enhance the immune response to cancer, immune therapies seek to either induce high avidity immune responses to tumour specific antigens or [...] Read more.
The interaction of the immune system with cancer is complex, but new approaches are resulting in exciting therapeutic benefits. In order to enhance the immune response to cancer, immune therapies seek to either induce high avidity immune responses to tumour specific antigens or to convert the tumour to a more pro-inflammatory microenvironment. Strategies, including vaccination, oncolytic viruses, and adoptive cell transfer all seek to induce anti-tumour immunity. To overcome the suppressive tumour microenvironment checkpoint inhibitors and modulators of regulatory cell populations have been investigated. This review summarizes the recent advances in immune therapies and discusses the importance of combination therapies in the treatment of cancers. Full article
(This article belongs to the Special Issue Dissecting the Immunological Landscape of Human Malignancies)
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Graphical abstract

14 pages, 3528 KiB  
Review
Immune Monitoring of Cancer Patients Prior to and During CTLA-4 or PD-1/PD-L1 Inhibitor Treatment
by Antje Tunger, Maximilian Kießler, Rebekka Wehner, Achim Temme, Friedegund Meier, Michael Bachmann and Marc Schmitz
Biomedicines 2018, 6(1), 26; https://doi.org/10.3390/biomedicines6010026 - 1 Mar 2018
Cited by 17 | Viewed by 7062
Abstract
Targeting the immune checkpoint receptors cytotoxic T lymphocyte antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1), or programmed cell death 1 ligand 1 (PD-L1) represents a very attractive treatment modality for tumor patients. The administration of antibodies against these receptors can promote [...] Read more.
Targeting the immune checkpoint receptors cytotoxic T lymphocyte antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1), or programmed cell death 1 ligand 1 (PD-L1) represents a very attractive treatment modality for tumor patients. The administration of antibodies against these receptors can promote efficient antitumor effects and can induce objective clinical responses in about 20–40% patients with various tumor types, accompanied by improved survival. Based on their therapeutic efficiency, several antibodies have been approved for the treatment of tumor patients. However, many patients do not respond to checkpoint inhibitor therapy. Therefore, the identification of biomarkers is required to guide patient selection for this treatment modality. Here, we summarize recent studies investigating the PD-L1 expression or mutational load of tumor tissues as well as the frequency and phenotype of immune cells in tumor patients prior to and during CTLA-4 or PD-1/PD-L1 inhibitor treatment. Full article
(This article belongs to the Special Issue Dissecting the Immunological Landscape of Human Malignancies)
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Graphical abstract

18 pages, 928 KiB  
Review
The Peripheral and Intratumoral Immune Cell Landscape in Cancer Patients: A Proxy for Tumor Biology and a Tool for Outcome Prediction
by Annette Schnell, Christian Schmidl, Wolfgang Herr and Peter J. Siska
Biomedicines 2018, 6(1), 25; https://doi.org/10.3390/biomedicines6010025 - 24 Feb 2018
Cited by 23 | Viewed by 6139
Abstract
Functional systemic and local immunity is required for effective anti-tumor responses. In addition to an active engagement with cancer cells and tumor stroma, immune cells can be affected and are often found to be dysregulated in cancer patients. The impact of tumors on [...] Read more.
Functional systemic and local immunity is required for effective anti-tumor responses. In addition to an active engagement with cancer cells and tumor stroma, immune cells can be affected and are often found to be dysregulated in cancer patients. The impact of tumors on local and systemic immunity can be assessed using a variety of approaches ranging from low-dimensional analyses that are performed on large patient cohorts to multi-dimensional assays that are technically and logistically challenging and are therefore confined to a limited sample size. Many of these strategies have been established in recent years leading to exciting findings. Not only were analyses of immune cells in tumor patients able to predict the clinical course of the disease and patients’ survival, numerous studies also detected changes in the immune landscape that correlated with responses to novel immunotherapies. This review will provide an overview of established and novel tools for assessing immune cells in tumor patients and will discuss exemplary studies that utilized these techniques to predict patient outcomes. Full article
(This article belongs to the Special Issue Dissecting the Immunological Landscape of Human Malignancies)
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Figure 1

12 pages, 2705 KiB  
Review
Immune Landscape of Breast Cancers
by Divya Nagarajan and Stephanie E. B. McArdle
Biomedicines 2018, 6(1), 20; https://doi.org/10.3390/biomedicines6010020 - 11 Feb 2018
Cited by 93 | Viewed by 12139
Abstract
Breast cancer is a very heterogeneous disease, both at a molecular and a histological level. Five intrinsic subtypes were initially identified—Luminal-A, Luminal-B, HER2+, Triple negative/basal like (TNBC) and normal like—subsequently expanded to seven (Basal-like-1 and 2, mesenchymal, mesenchymal stem-like, luminal androgen [...] Read more.
Breast cancer is a very heterogeneous disease, both at a molecular and a histological level. Five intrinsic subtypes were initially identified—Luminal-A, Luminal-B, HER2+, Triple negative/basal like (TNBC) and normal like—subsequently expanded to seven (Basal-like-1 and 2, mesenchymal, mesenchymal stem-like, luminal androgen receptor, immuno-modulatory and unstable). Although genetic and epigenetic changes are key pathogenic events, the immune system plays a substantial role in promoting progression and metastasis. This review will discuss the extent to which immune cells can be detected within the tumor microenvironment, as well as their prognostic role and relationship with the microbiome, with an emphasis on TNBC. Full article
(This article belongs to the Special Issue Dissecting the Immunological Landscape of Human Malignancies)
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Graphical abstract

11 pages, 605 KiB  
Review
Bringing the Next Generation of Immuno-Oncology Biomarkers to the Clinic
by Alessandra Cesano and Sarah Warren
Biomedicines 2018, 6(1), 14; https://doi.org/10.3390/biomedicines6010014 - 2 Feb 2018
Cited by 56 | Viewed by 14792
Abstract
The recent successes in the use of immunotherapy to treat cancer have led to a multiplicity of new compounds in development. Novel clinical-grade biomarkers are needed to guide the choice of these agents to obtain the maximal likelihood of patient benefit. Predictive biomarkers [...] Read more.
The recent successes in the use of immunotherapy to treat cancer have led to a multiplicity of new compounds in development. Novel clinical-grade biomarkers are needed to guide the choice of these agents to obtain the maximal likelihood of patient benefit. Predictive biomarkers for immunotherapy differ from the traditional biomarkers used for targeted therapies: the complexity of the immune response and tumour biology requires a more holistic approach than the use of a single analyte biomarker. This paper reviews novel biomarker approaches for the effective development of immune-oncology therapies, highlighting the promise of the advances in next-generation gene expression profiling that allow biologic information to be efficiently organized and interpreted for a maximum predictive value at the individual patient level. Full article
(This article belongs to the Special Issue Dissecting the Immunological Landscape of Human Malignancies)
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