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Cancers
Special Issues
Regulatory T Cells in Tumor Environment
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Regulatory T Cells in Tumor Environment

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 March 2023) | Viewed by 18435

Special Issue Editor

Dr. Christine Ménétrier-Caux

E-Mail Website
Guest Editor
Cancer Research Center Lyon, UMR INSERM 1052 CNRS 5286, Centre Léon Bérard, 28 rue Laennec, 69373 Lyon, France
Interests: regulatory T cells; effector T cells; immunotherapies; adenosine metabolism, Th1.17

Special Issue Information

Dear Colleagues,

Regulatory T cells (Tregs), an immunosuppressive subset of CD4+ T cells characterized by the master transcription factor FoxP3, play essential roles in maintaining self-tolerance. In cancer patients, Tregs are major players in hampering effective anti-tumor immunity, favoring tumor development and progression. Based on FoxP3, the prognosis impact of Tregs in tumors has been well described. However, recent single-cell transcriptomic data suggest a heterogeneity of this compartment in tumors, possibly resulting in unique functions. The objective of this Special Issue is to gather original studies and reviews addressing the new knowledge available on Tregs in the tumor environment to better apprehend their diversity and functions and identify new specific therapeutic targets.

This Special Issue is expected to assemble studies analyzing the prognosis value of Tregs, the mechanisms involved in their recruitment and expansion in the tumor environment, their localization and residency, as well as their heterogeneity (transcriptome, phenotype, activation/exhaustion, function, origin (natural/induced)). Of specific interest are reports on Treg stability, molecular regulation, expansion, metabolism, antigen specificity, and new mechanisms of the suppression of Tregs in the tumor environment. Despite the clinical efficacy of several drugs targeting inhibitory immune checkpoints (ICPs) (anti-CTLA-4, anti-PD1/PDL1) in solid tumors, resistance or hyper-progression occur. Reports investigating the involvement of Tregs in the efficacy of or resistance to these treatments are welcome. Finally, the characterization of markers delineating tumor-infiltrating Tregs from other tissue-Treg and T-cell effectors would help in defining new immunotherapeutic approaches to specifically target Tregs in the tumor environment to avoid severe autoimmune side effects.

Dr. Christine Ménétrier-Caux
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

  • Tregs
  • stability
  • heterogeneity
  • molecular regulation
  • prognostic factor
  • metabolism
  • immunotherapy
  • new target discovery

Published Papers (3 papers)

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Review

49 pages, 4252 KiB  
Review
Recruitment and Expansion of Tregs Cells in the Tumor Environment—How to Target Them?
by Justine Cinier, Margaux Hubert, Laurie Besson, Anthony Di Roio, Céline Rodriguez, Vincent Lombardi, Christophe Caux and Christine Ménétrier-Caux
Cancers 2021, 13(8), 1850; https://doi.org/10.3390/cancers13081850 - 13 Apr 2021
Cited by 38 | Viewed by 6508
Abstract
Regulatory T cells (Tregs) are present in a large majority of solid tumors and are mainly associated with a poor prognosis, as their major function is to inhibit the antitumor immune response contributing to immunosuppression. In this review, we will investigate the mechanisms [...] Read more.
Regulatory T cells (Tregs) are present in a large majority of solid tumors and are mainly associated with a poor prognosis, as their major function is to inhibit the antitumor immune response contributing to immunosuppression. In this review, we will investigate the mechanisms involved in the recruitment, amplification and stability of Tregs in the tumor microenvironment (TME). We will also review the strategies currently developed to inhibit Tregs’ deleterious impact in the TME by either inhibiting their recruitment, blocking their expansion, favoring their plastic transformation into other CD4+ T-cell subsets, blocking their suppressive function or depleting them specifically in the TME to avoid severe deleterious effects associated with Treg neutralization/depletion in the periphery and normal tissues. Full article
(This article belongs to the Special Issue Regulatory T Cells in Tumor Environment)
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19 pages, 2118 KiB  
Review
Hyper-Progressive Disease: The Potential Role and Consequences of T-Regulatory Cells Foiling Anti-PD-1 Cancer Immunotherapy
by Christopher Tay, Yamin Qian and Shimon Sakaguchi
Cancers 2021, 13(1), 48; https://doi.org/10.3390/cancers13010048 - 26 Dec 2020
Cited by 17 | Viewed by 6942
Abstract
Antibody-mediated disruption of the programmed cell death protein 1 (PD-1) pathway has brought much success to the fight against cancer. Nevertheless, a significant proportion of patients respond poorly to anti-PD-1 treatment. Cases of accelerated and more aggressive forms of cancer following therapy have [...] Read more.
Antibody-mediated disruption of the programmed cell death protein 1 (PD-1) pathway has brought much success to the fight against cancer. Nevertheless, a significant proportion of patients respond poorly to anti-PD-1 treatment. Cases of accelerated and more aggressive forms of cancer following therapy have also been reported. Termed hyper-progressive disease (HPD), this phenomenon often results in fatality, thus requires urgent attention. Among possible causes of HPD, regulatory T-cells (Tregs) are of suspect due to their high expression of PD-1, which modulates Treg activity. Tregs are a subset of CD4+ T-cells that play a non-redundant role in the prevention of autoimmunity and is functionally dependent on the X chromosome-linked transcription factor FoxP3. In cancer, CD4+FoxP3+ Tregs migrate to tumors to suppress anti-tumor immune responses, allowing cancer cells to persist. Hence, Treg accumulation in tumors is associated with poor prognosis. In mice, the anti-tumor efficacy of anti-PD-1 can be enhanced by depleting Tregs. This suggests Tregs pose resistance to anti-PD-1 therapy. In this article, we review the relevant Treg functions that suppress tumor immunity and the potential effects anti-PD-1 could have on Tregs which are counter-productive to the treatment of cancer, occasionally causing HPD. Full article
(This article belongs to the Special Issue Regulatory T Cells in Tumor Environment)
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20 pages, 1126 KiB  
Review
Transcriptional Control of Regulatory T Cells in Cancer: Toward Therapeutic Targeting?
by Pierre Stéphan, Raphaëlle Lautraite, Allison Voisin and Yenkel Grinberg-Bleyer
Cancers 2020, 12(11), 3194; https://doi.org/10.3390/cancers12113194 - 30 Oct 2020
Cited by 6 | Viewed by 3158
Abstract
Extensive research in the past decades has highlighted the tight link between immunity and cancer, leading to the development of immunotherapies that have revolutionized cancer care. However, only a fraction of patients display durable responses to these treatments, and a deeper understanding of [...] Read more.
Extensive research in the past decades has highlighted the tight link between immunity and cancer, leading to the development of immunotherapies that have revolutionized cancer care. However, only a fraction of patients display durable responses to these treatments, and a deeper understanding of the cellular and mechanisms orchestrating immune responses to tumors is mandatory for the discovery of novel therapeutic targets. Among the most scrutinized immune cells, Forkhead Box Protein P3 (Foxp3)+ Regulatory T cells (Treg cells) are central inhibitors of protective anti-tumor immunity. These tumor-promoting functions render Treg cells attractive immunotherapy targets, and multiple strategies are being developed to inhibit their recruitment, survival, and function in the tumor microenvironment. In this context, it is critical to decipher the complex and multi-layered molecular mechanisms that shape and stabilize the Treg cell transcriptome. Here, we provide a global view of the transcription factors, and their upstream signaling pathways, involved in the programming of Treg cell homeostasis and functions in cancer. We also evaluate the feasibility and safety of novel therapeutic approaches aiming at targeting specific transcriptional regulators. Full article
(This article belongs to the Special Issue Regulatory T Cells in Tumor Environment)
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