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New Insights in Immune Cell Diversity: A Bridge Between the Patient Stratification and Personalized Therapies

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

Deadline for manuscript submissions: closed (30 November 2020) | Viewed by 15064

Special Issue Editors


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Guest Editor
Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
Interests: microbiota-immunity axis; autoimmunity; cancers; inflammation; T cells; micro and nanoplastic effects on human
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Guest Editor
Institut d’Investigació Sanitària Illes Balears (IdISBa, Health Research Institute of the Balearic Islands), 07120 Palma, Spain
Interests: membrane lipidome; imaging mass spectrometry; inflammatory bowel disease; colorectal cancer; lipid fingerprint; lipid biomarkers; lipid pharmacological targets
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In recent years, there have been significant advances in the understanding of the human immune system and of the impact it has on different diseases. Two factors account for this considerable progress. First, the new technological developments, such as mass cytometry, single-cell immunogenomics, and system biology approaches, allow analyses with unprecedented resolution at the cellular level of the immune compartment. This has led to a highly dynamic situation in which new immune populations are constantly identified and described.

Second, increasing evidence is unveiling the intricate networks involved in immune recognition and tissue homeostasis. As has long been known and then confirmed, the immune system comprises an extraordinary diversity of cell types acting together to accomplish their complex biological functions. Indeed, the immune response plays a critical role in pathological situations, such as cancer, chronic inflammation, autoimmunity, and diseases associated with metabolic imbalance (diabetes, obesity) and neurological (neurodegenerative or mood) disorders, where tissue homeostasis is highly compromised. Hence, no doubt, the characterization of the immune compartment will be of great relevance for patient stratification and prognosis. Therefore, all the information gathered in this context will be critical for leading novel immunotherapies closer to daily clinical practice and personalized therapies.

This Special Issue aims to highlight the research and strategies currently used to redefine the cellular diversity within the immune system. It also welcomes all those studies seeking not only to elucidate how the immune system participates in tissue homeostasis and disease but also to improve the current immune-based scores tools for prognosis and patient stratification, which will eventually help to outline novel strategies to address personalized treatments.

Prof. Dr. Amedeo Amedei
Dr. Gwendolyn Barceló-Coblijng
Guest Editors

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Keywords

  • Immunity
  • Immune cells
  • Immune Response
  • Immunotherapy
  • Immunoscore

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Published Papers (3 papers)

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Research

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18 pages, 3342 KiB  
Article
Retinal Pigment Epithelial Cells Derived from Induced Pluripotent Stem (iPS) Cells Suppress or Activate T Cells via Costimulatory Signals
by Sunao Sugita, Yoko Futatsugi, Masaaki Ishida, Ayaka Edo and Masayo Takahashi
Int. J. Mol. Sci. 2020, 21(18), 6507; https://doi.org/10.3390/ijms21186507 - 5 Sep 2020
Cited by 14 | Viewed by 3590
Abstract
Human retinal pigment epithelial (RPE) cells derived from induced pluripotent stem (iPS) cells have immunosuppressive properties. However, RPE cells are also known as immunogenic cells, and they have major histocompatibility complex expression and produce inflammatory proteins, and thus experience immune rejection after transplantation. [...] Read more.
Human retinal pigment epithelial (RPE) cells derived from induced pluripotent stem (iPS) cells have immunosuppressive properties. However, RPE cells are also known as immunogenic cells, and they have major histocompatibility complex expression and produce inflammatory proteins, and thus experience immune rejection after transplantation. In this study, to confirm the immunological properties of IPS-RPE cells, we examined whether human RPE cells derived from iPS cells could suppress or stimulate inflammatory T cells from uveitis patients via costimulatory signals. We established T cells from patients with active uveitis as target cells and used iPS-RPE cells as effector cells. As a result, cultured iPS-RPE cells inhibited cell proliferation and the production of IFN-γ by activated uveitis CD4+ T cells, especially Th1-type T cells. In contrast, iPS-RPE cells stimulated T cells of uveitis patients. The iPS-RPE cells constitutively expressed B7-H1/CD274 and B7-DC/CD273, and suppressed the activation of T cells via the PD-1 receptor. iPS-RPE expressed these negative costimulatory molecules, especially when RPE cells were pretreated with recombinant IFN-γ. In addition, iPS-RPE cells also expressed B7-H3/CD276 costimulatory molecules and activated uveitis T cells through the B7-H3-TLT-2 receptor. Thus, cultured iPS-derived retinal cells can suppress or activate inflammatory T cells in vitro through costimulatory interactions. Full article
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16 pages, 4398 KiB  
Article
A Strategy for Personalized Treatment of iPS-Retinal Immune Rejections Assessed in Cynomolgus Monkey Models
by Shota Fujii, Sunao Sugita, Yoko Futatsugi, Masaaki Ishida, Ayaka Edo, Kenichi Makabe, Hiroyuki Kamao, Yuko Iwasaki, Hirokazu Sakaguchi, Yasuhiko Hirami, Yasuo Kurimoto and Masayo Takahashi
Int. J. Mol. Sci. 2020, 21(9), 3077; https://doi.org/10.3390/ijms21093077 - 27 Apr 2020
Cited by 20 | Viewed by 4643
Abstract
Recently, we successfully transplanted an autograft, or major histocompatibility complex (MHC)-matched allografts, from induced-pluripotent-stem-cell-derived retinal pigment epithelial (iPSC-RPE) cells in patients with age-related macular degeneration. However, there was an issue regarding immune rejection after transplantation. In this study, we established a preoperational in [...] Read more.
Recently, we successfully transplanted an autograft, or major histocompatibility complex (MHC)-matched allografts, from induced-pluripotent-stem-cell-derived retinal pigment epithelial (iPSC-RPE) cells in patients with age-related macular degeneration. However, there was an issue regarding immune rejection after transplantation. In this study, we established a preoperational in vitro “drug–lymphocytes–grafts immune reaction (Drug-LGIR)” test to determine the medication for immune rejection using host immunocompetent cells (lymphocytes) and transplant cells (target iPSC-RPE cells) together with different medications. The adequacy of the test was assessed by in vivo transplantation in monkey models together with medication based on in vitro data. In the results of Drug-LGIR tests, some drugs exhibited significant suppression of RPE cell-related allogeneic reactions, while other drugs did not, and the efficacy of each drug differed among the recipient monkeys. Based on the results of Drug-LGIR, we applied cyclosporine A or local steroid (triamcinolone) therapy to two monkeys, and successfully suppressed RPE-related immune rejections with RPE grafts, which survived without any signs of rejection under drug administration. We propose that our new preoperational in vitro Drug-LGIR test, which specifies the most efficacious medication for each recipient, is useful for controlling immune attacks with personalized treatment for each patient after retinal transplantation. Full article
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Review

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14 pages, 791 KiB  
Review
Immune Landscape in Tumor Microenvironment: Implications for Biomarker Development and Immunotherapy
by Karim Pérez-Romero, Ramón M. Rodríguez, Amedeo Amedei, Gwendolyn Barceló-Coblijn and Daniel H. Lopez
Int. J. Mol. Sci. 2020, 21(15), 5521; https://doi.org/10.3390/ijms21155521 - 1 Aug 2020
Cited by 29 | Viewed by 6072
Abstract
Integration of the tumor microenvironment as a fundamental part of the tumorigenic process has undoubtedly revolutionized our understanding of cancer biology. Increasing evidence indicates that neoplastic cells establish a dependency relationship with normal resident cells in the affected tissue and, furthermore, develop the [...] Read more.
Integration of the tumor microenvironment as a fundamental part of the tumorigenic process has undoubtedly revolutionized our understanding of cancer biology. Increasing evidence indicates that neoplastic cells establish a dependency relationship with normal resident cells in the affected tissue and, furthermore, develop the ability to recruit new accessory cells that aid tumor development. In addition to normal stromal and tumor cells, this tumor ecosystem includes an infiltrated immune component that establishes complex interactions that have a critical effect during the natural history of the tumor. The process by which immune cells modulate tumor progression is known as immunoediting, a dynamic process that creates a selective pressure that finally leads to the generation of immune-resistant cells and the inability of the immune system to eradicate the tumor. In this context, the cellular and functional characterization of the immune compartment within the tumor microenvironment will help to understand tumor progression and, ultimately, will serve to create novel prognostic tools and improve patient stratification for cancer treatment. Here we review the impact of the immune system on tumor development, focusing particularly on its clinical implications and the current technologies used to analyze immune cell diversity within the tumor. Full article
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