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Cancers
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Blood Immune Cell and Cancer Therapeutics
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Blood Immune Cell and Cancer Therapeutics

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (31 October 2021) | Viewed by 7847

Special Issue Editor

Dr. Dagmar Riemann

E-Mail Website
Guest Editor
Institute of Medical Immunology, Martin Luther University Halle-Wittenberg, 06112 Halle, Germany
Interests: tumor-infiltrating lymphocytes; immunodeficiency; multi-color flow cytometry; myeloid suppressor cells; immunomonitoring

Special Issue Information

Dear Colleagues,

Immune cells possess effective tools to combat cancer cells, but can succumb in the battle. Therefore, a major focus in oncology has become the identification and development of therapeutics to overcome the mechanisms of cancer-induced immune suppression. Since the clinical responses to these treatments are often limited and currently unpredictable, there is an urgent need to identify potential biomarkers that predict the response to therapy and enable the early detection of treatment resistances. Immune monitoring may help in guiding treatment decisions or might prevent adverse effects associated with tumor therapy. Analyzing peripheral blood as a minimally invasive approach is critical for developing biomarkers with clinical utility. A broad spectrum of immune-related parameters can be measured, including the blood immune cell repertoire and its functional aspects. Ideal biomarkers will need to be comprehensive and multifaceted. Immune signatures can be monitored using different “omics”-based technologies, tetramer and ELIspot methods, or new flow cytometry techniques such as mass cytometry.

Important challenges exist in bridging the gap between identifying signatures correlated with therapy response/nonresponse and validated biomarker selection. Biomarker development depends on having standardized, reproducible, and feasible assays with clearly defined cutoff values and with a high sensitivity and specificity. This Special Issue will highlight key findings correlating blood immune cell characteristics at baseline or on-treatment with patients’ response to cancer treatment.

Dr. Dagmar Riemann
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. 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

  • biomarker
  • blood immune cells
  • flow cytometry
  • gene profiling
  • immunomonitoring
  • immunotherapy
  • tetramer assay
  • therapy resistance

Published Papers (3 papers)

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Research

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16 pages, 1584 KiB  
Article
Blood Immune Cell Biomarkers in Lung Cancer Patients Undergoing Treatment with a Combination of Chemotherapy and Immune Checkpoint Blockade
by Miriam Möller, Steffi Turzer, Georgi Ganchev, Andreas Wienke, Wolfgang Schütte, Barbara Seliger and Dagmar Riemann
Cancers 2022, 14(15), 3690; https://doi.org/10.3390/cancers14153690 - 28 Jul 2022
Cited by 6 | Viewed by 1711
Abstract
Although immune checkpoint inhibitor (ICI) therapies have improved the treatment of patients with advanced non-small cell lung cancer (NSCLC), several patients do not achieve durable clinical responses. Biomarkers for the prediction of therapy responses are urgently needed. To identify blood cell parameters correlating [...] Read more.
Although immune checkpoint inhibitor (ICI) therapies have improved the treatment of patients with advanced non-small cell lung cancer (NSCLC), several patients do not achieve durable clinical responses. Biomarkers for the prediction of therapy responses are urgently needed. To identify blood cell parameters correlating with patients’ survival, immune cells from 90 patients with NSCLC undergoing a combination of ICI and chemotherapy were prospectively monitored. At the time point of the first and third antibody administration, complete leukocyte blood count, the percentage of HLA-DRlow monocytes, the percentage of 6-Sulfo LacNAc (slan)+CD16+ non-classical monocytes, and the number of circulating dendritic cell (DC) subtypes, as well as T-, B-, and NK cells were determined by multi-color flow cytometry in peripheral blood. The prognostic value of the immune cell parameters investigated was evaluated by patients’ survival analysis, with progression-free survival (PFS) as the main criterion. A total of 67 patients (74.4%) showed a partial remission or a stable disease, and 35% of patients even survived 12 months and longer. Patients with a neutrophil-to-lymphocyte ratio (NLR) ≥6.1, a frequency of HLA-DRlow monocytes ≥22%, of slan+ non-classical monocytes <0.25% of leukocytes, and/or a sum of myeloid DC (MDC) and plasmacytoid DC (PDC) ≤0.14% of leukocytes had a poorer prognosis. The hazard ratio for PFS was 2.097 (1.208–3.640) for the NLR, 1.964 (1.046–3.688) for HLA-DRlow monocytes, 3.202 (1.712–5.99) for slan+ non-classical monocytes, and 2.596 (1.478–4.56) for the MDC/PDC sum. Patients without any of the four risk factors showed the best PFS. Furthermore, low NK cell counts correlated with shorter PFS (cutoff 200 cells/µL). Female patients had lower baseline NK cell counts and a shorter PFS. Our study confirms the usefulness of blood immune cells as biomarkers for clinical response and survival in NSCLC patients undergoing a combined ICI/chemotherapy. Full article
(This article belongs to the Special Issue Blood Immune Cell and Cancer Therapeutics)
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21 pages, 3137 KiB  
Article
Using a Prime-Boost Vaccination Strategy That Proved Effective for High Resolution Epitope Mapping to Characterize the Elusive Immunogenicity of Survivin
by Robert C. Mould, Jacob P. van Vloten, Amanda W. K. AuYeung, Scott R. Walsh, Jondavid de Jong, Leonardo Susta, Anthony J. Mutsaers, James J. Petrik, Geoffrey A. Wood, Sarah K. Wootton, Khalil Karimi and Byram W. Bridle
Cancers 2021, 13(24), 6270; https://doi.org/10.3390/cancers13246270 - 14 Dec 2021
Viewed by 2106
Abstract
Survivin is a member of the inhibitor of apoptosis family of proteins and has been reported to be highly expressed in a variety of cancer types, making it a high priority target for cancer vaccination. We previously described a heterologous prime-boost strategy using [...] Read more.
Survivin is a member of the inhibitor of apoptosis family of proteins and has been reported to be highly expressed in a variety of cancer types, making it a high priority target for cancer vaccination. We previously described a heterologous prime-boost strategy using a replication-deficient adenovirus, followed by an oncolytic rhabdovirus that generates unprecedented antigen-specific T cell responses. We engineered each vector to express a mutated version of full-length murine survivin. We first sought to uncover the complete epitope map for survivin-specific T cell responses in C57BL/6 and BALB/c mice by flow cytometry. However, no T cell responses were detected by intracellular cytokine staining after re-stimulation of T cells. Survivin has been found to be expressed by activated T cells, which could theoretically cause T cell-mediated killing of activated T cells, known as fratricide. We were unable to recapitulate this phenomenon in experiments. Interestingly, the inactivated survivin construct has been previously shown to directly kill tumor cells in vitro. However, there was no evidence in our models of induction of death in antigen-presenting cells due to treatment with a survivin-expressing vector. Using the same recombinant virus-vectored prime-boost strategy targeting the poorly immunogenic enhanced green fluorescent protein proved to be a highly sensitive method for mapping T cell epitopes, particularly in the context of identifying novel epitopes recognized by CD4+ T cells. Overall, these results suggested there may be unusually robust tolerance to survivin in commonly used mouse strains that cannot be broken, even when using a particularly potent vaccination platform. However, the vaccination method shows great promise as a strategy for identifying novel and subdominant T cell epitopes. Full article
(This article belongs to the Special Issue Blood Immune Cell and Cancer Therapeutics)
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Review

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32 pages, 1972 KiB  
Review
The Dual Role of Innate Lymphoid and Natural Killer Cells in Cancer. from Phenotype to Single-Cell Transcriptomics, Functions and Clinical Uses
by Stefania Roma, Laura Carpen, Alessandro Raveane and Francesco Bertolini
Cancers 2021, 13(20), 5042; https://doi.org/10.3390/cancers13205042 - 9 Oct 2021
Cited by 7 | Viewed by 3499
Abstract
The role of innate lymphoid cells (ILCs), including natural killer (NK) cells, is pivotal in inflammatory modulation and cancer. Natural killer cell activity and count have been demonstrated to be regulated by the expression of activating and inhibitory receptors together with and as [...] Read more.
The role of innate lymphoid cells (ILCs), including natural killer (NK) cells, is pivotal in inflammatory modulation and cancer. Natural killer cell activity and count have been demonstrated to be regulated by the expression of activating and inhibitory receptors together with and as a consequence of different stimuli. The great majority of NK cell populations have an anti-tumor activity due to their cytotoxicity, and for this reason have been used for cellular therapies in cancer patients. On the other hand, the recently classified helper ILCs are fundamentally involved in inflammation and they can be either helpful or harmful in cancer development and progression. Tissue niche seems to play an important role in modulating ILC function and conversion, as observed at the transcriptional level. In the past, these cell populations have been classified by the presence of specific cellular receptor markers; more recently, due to the advent of single-cell RNA sequencing (scRNA-seq), it has been possible to also explore them at the transcriptomic level. In this article we review studies on ILC (and NK cell) classification, function and their involvement in cancer. We also summarize the potential application of NK cells in cancer therapy and give an overview of the most recent studies involving ILCs and NKs at scRNA-seq, focusing on cancer. Finally, we provide a resource for those who wish to start single-cell transcriptomic analysis on the context of these innate lymphoid cell populations. Full article
(This article belongs to the Special Issue Blood Immune Cell and Cancer Therapeutics)
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