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T Cells and Innate Lymphoid Cells in the Immune Response against Hematological Malignancies

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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 June 2021) | Viewed by 11137

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Special Issue Editors

Prof. Dr. Antonio F. Campese

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Guest Editor

Department of Molecular Medicine, ‘Sapienza’, University of Rome, 00161 Rome, Italy
Interests: T cell development/differentiation; T cell leukemia; Notch signaling; regulatory T cells; myeloid derived suppressor cells; tumor immunology; autoimmunity
Special Issues, Collections and Topics in MDPI journals

Dr. Giovanni Bernardini

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Guest Editor

Department of Molecular Medicine, ‘Sapienza’, University of Rome, 00161 Rome, Italy
Interests: immune cell migration; natural killer cells; multiple myeloma; chemokines; GPCR signaling; ILC/myeloid cell cross-talk

Special Issue Information

Dear Colleagues,

During the last two decades, the microenvironmental issue has been recognized as a crucial part of cancer-related processes. In this context, the immune response of innate and adaptive origins against tumors seems to be an equalizer in determining the fate of cancer cells. Immune cell subsets, belonging to the T cells and innate lymphoid cells (ILC), including natural killer cells, are the subject of intense studies concerning the tumorigenesis, progression, and therapy of different hematological malignancies. Considerable efforts are being dedicated to identifying therapeutic strategies to overcome tumor immune evasion, as well as modifying T and NK cells to enhance their capacity to reach tumor sites and recognize tumor cells.

This Special Issue will be devoted to collecting original research papers, as well as reviews, focused on exploring the crosstalk between hematopoietic cancer cells and immune T or innate lymphoid cells from multiple points of view, including, but not limited to, the bidirectional influence exerted on tumor development/progression, on one side, and on polarization/function/cell-to-cell signaling, on the other side. We also welcome manuscripts related to the potential therapeutic fallout of strategies to boost T and innate lymphoid cell activation, with particular regard to those that impact immuno-suppression and immuno-evasion processes.

Dr. Antonio F. Campese
Dr. Giovanni Bernardini
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 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. 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

T cells
NK cells
innate lymphoid cells
anti-tumor immune response
immuno-suppression
immuno-evasion
chemokine/cytokines
hematological malignancies
immune checkpoints

Published Papers (3 papers)

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Research

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15 pages, 3753 KiB

Open AccessArticle

Preclinical Evaluation of Invariant Natural Killer T Cells Modified with CD38 or BCMA Chimeric Antigen Receptors for Multiple Myeloma

by Renée Poels, Esther Drent, Roeland Lameris, Afroditi Katsarou, Maria Themeli, Hans J. van der Vliet, Tanja D. de Gruijl, Niels W. C. J. van de Donk and Tuna Mutis

Int. J. Mol. Sci. 2021, 22(3), 1096; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22031096 - 22 Jan 2021

Cited by 27 | Viewed by 4143

Abstract

Due to the CD1d restricted recognition of altered glycolipids, Vα24-invariant natural killer T (iNKT) cells are excellent tools for cancer immunotherapy with a significantly reduced risk for graft-versus-host disease when applied as off-the shelf-therapeutics across Human Leukocyte Antigen (HLA) barriers. To maximally harness their therapeutic potential for multiple myeloma (MM) treatment, we here armed iNKT cells with chimeric antigen receptors (CAR) directed against the MM-associated antigen CD38 and the plasma cell specific B cell maturation antigen (BCMA). We demonstrate that both CD38- and BCMA-CAR iNKT cells effectively eliminated MM cells in a CAR-dependent manner, without losing their T cell receptor (TCR)-mediated cytotoxic activity. Importantly, iNKT cells expressing either BCMA-CARs or affinity-optimized CD38-CARs spared normal hematopoietic cells and displayed a Th1-like cytokine profile, indicating their therapeutic utility. While the costimulatory domain of CD38-CARs had no influence on the cytotoxic functions of iNKT cells, CARs containing the 4-1BB domain showed a better expansion capacity. Interestingly, when stimulated only via CD1d⁺ dendritic cells (DCs) loaded with α-galactosylceramide (α-GalCer), both CD38- and BCMA-CAR iNKT cells expanded well, without losing their CAR- or TCR-dependent cytotoxic activities. This suggests the possibility of developing an off-the-shelf therapy with CAR iNKT cells, which might even be boostable in vivo by administration α-GalCer pulsed DCs. Full article

(This article belongs to the Special Issue T Cells and Innate Lymphoid Cells in the Immune Response against Hematological Malignancies)

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Review

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19 pages, 768 KiB

Open AccessReview

MicroRNAs as Modulators of the Immune Response in T-Cell Acute Lymphoblastic Leukemia

by Martina Del Gaizo, Ilaria Sergio, Sara Lazzari, Samantha Cialfi, Maria Pelullo, Isabella Screpanti and Maria Pia Felli

Int. J. Mol. Sci. 2022, 23(2), 829; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23020829 - 13 Jan 2022

Cited by 5 | Viewed by 2329

Abstract

Acute lymphoblastic leukaemia (ALL) is an aggressive haematological tumour driven by the malignant transformation and expansion of B-cell (B-ALL) or T-cell (T-ALL) progenitors. The evolution of T-ALL pathogenesis encompasses different master developmental pathways, including the main role played by Notch in cell fate choices during tissue differentiation. Recently, a growing body of evidence has highlighted epigenetic changes, particularly the altered expression of microRNAs (miRNAs), as a critical molecular mechanism to sustain T-ALL. The immune response is emerging as key factor in the complex multistep process of cancer but the role of miRNAs in anti-leukaemia response remains elusive. In this review we analyse the available literature on miRNAs as tuners of the immune response in T-ALL, focusing on their role in Natural Killer, T, T-regulatory and Myeloid-derived suppressor cells. A better understanding of this molecular crosstalk may provide the basis for the development of potential immunotherapeutic strategies in the leukemia field. Full article

(This article belongs to the Special Issue T Cells and Innate Lymphoid Cells in the Immune Response against Hematological Malignancies)

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31 pages, 1815 KiB

Open AccessReview

NK Cells in Chronic Lymphocytic Leukemia and Their Therapeutic Implications

by Paolo Sportoletti, Filomena De Falco, Beatrice Del Papa, Stefano Baldoni, Valerio Guarente, Andrea Marra, Erica Dorillo, Chiara Rompietti, Francesco Maria Adamo, Loredana Ruggeri, Mauro Di Ianni and Emanuela Rosati

Int. J. Mol. Sci. 2021, 22(13), 6665; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22136665 - 22 Jun 2021

Cited by 12 | Viewed by 4068

Abstract

Key features of chronic lymphocytic leukemia (CLL) are defects in the immune system and the ability of leukemic cells to evade immune defenses and induce immunosuppression, resulting in increased susceptibility to infections and disease progression. Several immune effectors are impaired in CLL, including T and natural killer (NK) cells. The role of T cells in defense against CLL and in CLL progression and immunotherapy has been extensively studied. Less is known about the role of NK cells in this leukemia, and data on NK cell alterations in CLL are contrasting. Besides studies showing that NK cells have intrinsic defects in CLL, there is a large body of evidence indicating that NK cell dysfunctions in CLL mainly depend on the escape mechanisms employed by leukemic cells. In keeping, it has been shown that NK cell functions, including antibody-dependent cellular cytotoxicity (ADCC), can be retained and/or restored after adequate stimulation. Therefore, due to their preserved ADCC function and the reversibility of CLL-related dysfunctions, NK cells are an attractive source for novel immunotherapeutic strategies in this disease, including chimeric antigen receptor (CAR) therapy. Recently, satisfying clinical responses have been obtained in CLL patients using cord blood-derived CAR-NK cells, opening new possibilities for further exploring NK cells in the immunotherapy of CLL. However, notwithstanding the promising results of this clinical trial, more evidence is needed to fully understand whether and in which CLL cases NK cell-based immunotherapy may represent a valid, alternative/additional therapeutic option for this leukemia. In this review, we provide an overview of the current knowledge about phenotypic and functional alterations of NK cells in CLL and the mechanisms by which CLL cells circumvent NK cell-mediated immunosurveillance. Additionally, we discuss the potential relevance of using NK cells in CLL immunotherapy. Full article

(This article belongs to the Special Issue T Cells and Innate Lymphoid Cells in the Immune Response against Hematological Malignancies)

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