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Cancers
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Innate T Cells in Cancer Immunity
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Innate T Cells in Cancer Immunity

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Immunology and Immunotherapy".

Deadline for manuscript submissions: closed (31 July 2021) | Viewed by 26060

Special Issue Editor

Dr. Vasileios Bekiaris

E-Mail Website
Guest Editor
Department of Health Technology, Technical University of Denmark, Denmark
Interests: innate lymphocytes; gamma delta T cells; immune signaling; development

Special Issue Information

Dear Colleagues,

Although T cells are traditionally viewed as adaptive immune cells, a large body of evidence has defined many different T cell subsets that display bona fide innate functionality. Thus, we know that in both mice and humans, gamma delta (γδ) T cells, natural killer T (NKT) cells, and mucosal associated invariant T (MAIT) cells are all part of a diverse innate immune system. These lymphocytes are often the first responders during infection and inflammation and can promote type 1, type 2 or type 3 immune responses depending on the specific stimuli and microenvironment they encounter.

It has become clear that innate T cells of all the above lineages play an active role in tumor immunity and have been shown to have both pro- and antitumor properties. Therefore, detailed understanding of their role in cancer will provide new insights into immunity and disease pathogenesis, and, hopefully, will allow us to design more specific immunotherapies.

In this Special Issue, we are seeking articles (reviews or original research) on the biology of innate T cells in relation to cancer. This may include mechanistic studies on the pro- and antitumor properties of innate T cells, or their role in cancer immunotherapy.             

Dr. Vasileios Bekiaris
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 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

  • innate
  • T cells
  • cancer

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Published Papers (5 papers)

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Review

31 pages, 2378 KiB  
Review
The Diverse Roles of γδ T Cells in Cancer: From Rapid Immunity to Aggressive Lymphoma
by Susann Schönefeldt, Tamara Wais, Marco Herling, Satu Mustjoki, Vasileios Bekiaris, Richard Moriggl and Heidi A. Neubauer
Cancers 2021, 13(24), 6212; https://doi.org/10.3390/cancers13246212 - 9 Dec 2021
Cited by 17 | Viewed by 5238
Abstract
γδ T cells are unique players in shaping immune responses, lying at the intersection between innate and adaptive immunity. Unlike conventional αβ T cells, γδ T cells largely populate non-lymphoid peripheral tissues, demonstrating tissue specificity, and they respond to ligands in an MHC-independent [...] Read more.
γδ T cells are unique players in shaping immune responses, lying at the intersection between innate and adaptive immunity. Unlike conventional αβ T cells, γδ T cells largely populate non-lymphoid peripheral tissues, demonstrating tissue specificity, and they respond to ligands in an MHC-independent manner. γδ T cells display rapid activation and effector functions, with a capacity for cytotoxic anti-tumour responses and production of inflammatory cytokines such as IFN-γ or IL-17. Their rapid cytotoxic nature makes them attractive cells for use in anti-cancer immunotherapies. However, upon transformation, γδ T cells can give rise to highly aggressive lymphomas. These rare malignancies often display poor patient survival, and no curative therapies exist. In this review, we discuss the diverse roles of γδ T cells in immune surveillance and response, with a particular focus on cancer immunity. We summarise the intriguing dichotomy between pro- and anti-tumour functions of γδ T cells in solid and haematological cancers, highlighting the key subsets involved. Finally, we discuss potential drivers of γδ T-cell transformation, summarising the main γδ T-cell lymphoma/leukaemia entities, their clinical features, recent advances in mapping their molecular and genomic landscapes, current treatment strategies and potential future targeting options. Full article
(This article belongs to the Special Issue Innate T Cells in Cancer Immunity)
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19 pages, 1424 KiB  
Review
Inhibiting the Unconventionals: Importance of Immune Checkpoint Receptors in γδ T, MAIT, and NKT Cells
by Elisa Catafal-Tardos, Maria Virginia Baglioni and Vasileios Bekiaris
Cancers 2021, 13(18), 4647; https://doi.org/10.3390/cancers13184647 - 16 Sep 2021
Cited by 11 | Viewed by 5224
Abstract
In recent years, checkpoint inhibitor (CPI) therapy has shown promising clinical responses across a broad range of cancers. However, many patients remain unresponsive and there is need for improvement. CPI therapy relies on antibody-mediated neutralization of immune inhibitory or checkpoint receptors (ICRs) that [...] Read more.
In recent years, checkpoint inhibitor (CPI) therapy has shown promising clinical responses across a broad range of cancers. However, many patients remain unresponsive and there is need for improvement. CPI therapy relies on antibody-mediated neutralization of immune inhibitory or checkpoint receptors (ICRs) that constitutively suppress leukocytes. In this regard, the clinical outcome of CPI therapy has primarily been attributed to modulating classical MHC-restricted αβ T cell responses, yet, it will inevitably target most lymphoid (and many myeloid) populations. As such, unconventional non-MHC-restricted gamma delta (γδ) T, mucosal associated invariant T (MAIT) and natural killer T (NKT) cells express ICRs at steady-state and after activation and may thus be affected by CPI therapies. To which extent, however, remains unclear. These unconventional T cells are polyfunctional innate-like lymphocytes that play a key role in tumor immune surveillance and have a plethora of protective and pathogenic immune responses. The robust anti-tumor potential of γδ T, MAIT, and NKT cells has been established in a variety of preclinical cancer models and in clinical reports. In contrast, recent studies have documented a pro-tumor effect of innate-like T cell subsets that secrete pro-inflammatory cytokines. Consequently, understanding the mechanisms that regulate such T cells and their response to CPI is critical in designing effective cancer immunotherapies that favor anti-tumor immunity. In this Review, we will discuss the current understanding regarding the role of immune checkpoint regulation in γδ T, MAIT, and NKT cells and its importance in anti-cancer immunity. Full article
(This article belongs to the Special Issue Innate T Cells in Cancer Immunity)
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22 pages, 1799 KiB  
Review
Regulation and Functions of Protumoral Unconventional T Cells in Solid Tumors
by Emilie Barsac, Carolina de Amat Herbozo, Loïc Gonzalez, Thomas Baranek, Thierry Mallevaey and Christophe Paget
Cancers 2021, 13(14), 3578; https://doi.org/10.3390/cancers13143578 - 16 Jul 2021
Cited by 5 | Viewed by 3791
Abstract
The vast majority of studies on T cell biology in tumor immunity have focused on peptide-reactive conventional T cells that are restricted to polymorphic major histocompatibility complex molecules. However, emerging evidence indicated that unconventional T cells, including γδ T cells, natural killer T [...] Read more.
The vast majority of studies on T cell biology in tumor immunity have focused on peptide-reactive conventional T cells that are restricted to polymorphic major histocompatibility complex molecules. However, emerging evidence indicated that unconventional T cells, including γδ T cells, natural killer T (NKT) cells and mucosal-associated invariant T (MAIT) cells are also involved in tumor immunity. Unconventional T cells span the innate–adaptive continuum and possess the unique ability to rapidly react to nonpeptide antigens via their conserved T cell receptors (TCRs) and/or to activating cytokines to orchestrate many aspects of the immune response. Since unconventional T cell lineages comprise discrete functional subsets, they can mediate both anti- and protumoral activities. Here, we review the current understanding of the functions and regulatory mechanisms of protumoral unconventional T cell subsets in the tumor environment. We also discuss the therapeutic potential of these deleterious subsets in solid cancers and why further feasibility studies are warranted. Full article
(This article belongs to the Special Issue Innate T Cells in Cancer Immunity)
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11 pages, 1054 KiB  
Review
Mucosal Associated Invariant T Cells in Cancer-Friend or Foe?
by Chloe O’Neill, Féaron C. Cassidy, Donal O’Shea and Andrew E. Hogan
Cancers 2021, 13(7), 1582; https://doi.org/10.3390/cancers13071582 - 30 Mar 2021
Cited by 14 | Viewed by 3832
Abstract
Mucosal associated invariant T (MAIT) cells are a population of unconventional T cells which can bridge the innate and adaptive immune systems. Well-described roles for MAIT cells include host protection against invading bacteria, fungi and viruses. Upon activation, MAIT cells become prolific effector [...] Read more.
Mucosal associated invariant T (MAIT) cells are a population of unconventional T cells which can bridge the innate and adaptive immune systems. Well-described roles for MAIT cells include host protection against invading bacteria, fungi and viruses. Upon activation, MAIT cells become prolific effector cells, capable of producing a range of cytokines and lytic molecules. In addition to their anti-microbial role, MAIT cells have been implicated in immune responses to cancer, with opposing beneficial and pathogenic roles reported. On the one hand, MAIT cells can home to the site of the tumour in many human cancers and can produce anti-tumour molecules. On the other, MAIT cells can display defective phenotypes in certain cancers and produce pro-tumour molecules. In this review, we discuss the current literature on the diverse roles for MAIT cells in cancer, outlining their frequencies, functions and associations with N staging and prognosis. We also discuss potential mechanisms underpinning cancer-related alterations in MAIT cells and highlight therapeutic approaches to harness or target MAIT cells in cancer. Full article
(This article belongs to the Special Issue Innate T Cells in Cancer Immunity)
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Graphical abstract

23 pages, 1458 KiB  
Review
MAIT Cells: Partners or Enemies in Cancer Immunotherapy?
by Dasha T. Cogswell, Laurent Gapin, Heather M. Tobin, Martin D. McCarter and Richard P. Tobin
Cancers 2021, 13(7), 1502; https://doi.org/10.3390/cancers13071502 - 25 Mar 2021
Cited by 21 | Viewed by 6537
Abstract
A recent boom in mucosal-associated invariant T (MAIT) cell research has identified relationships between MAIT cell abundance, function, and clinical outcomes in various malignancies. As they express a variety of immune checkpoint receptors and ligands, and possess strong cytotoxic functions, MAIT cells are [...] Read more.
A recent boom in mucosal-associated invariant T (MAIT) cell research has identified relationships between MAIT cell abundance, function, and clinical outcomes in various malignancies. As they express a variety of immune checkpoint receptors and ligands, and possess strong cytotoxic functions, MAIT cells are an attractive new subject in the field of tumor immunology. MAIT cells are a class of innate-like T cells that express a semi-invariant T cell antigen receptor (TCR) that recognizes microbially derived non-peptide antigens presented by the non-polymorphic MHC class-1 like molecule, MR1. In this review, we outline the current (and often contradictory) evidence exploring MAIT cell biology and how MAIT cells impact clinical outcomes in different human cancers, as well as what role they may have in cancer immunotherapy. Full article
(This article belongs to the Special Issue Innate T Cells in Cancer Immunity)
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