The immunosuppressive tumour network: myeloid-derived suppressor cells, regulatory T cells and natural killer T cells
Dennis Lindau,Paul R. Gielen,Michiel Kroesen,Pieter Wesseling,Pieter Wesseling,Gosse J. Adema +5 more
TLDR
The cross‐talk between MDSCs and other immune cells is reviewed, focusing on Treg cells and NKT cells, and its impact on basic and applied cancer research and how targeting M DSCs may pave the way for future immunocombination therapies are considered.Abstract:
Myeloid-derived suppressor cells (MDSC) and regulatory T (Treg) cells are major components of the immune suppressive tumour microenvironment (TME). Both cell types expand systematically in preclinical tumour models and promote T-cell dysfunction that in turn favours tumour progression. Clinical reports show a positive correlation between elevated levels of both suppressors and tumour burden. Recent studies further revealed that MDSCs can modulate the de novo development and induction of Treg cells. The overlapping target cell population of Treg cells and MDSCs is indicative for the importance and flexibility of immune suppression under pathological conditions. It also suggests the existence of common pathways that can be used for clinical interventions aiming to manipulate the TME. Elimination or reprogramming of the immune suppressive TME is one of the major current challenges in immunotherapy of cancer. Interestingly, recent findings suggest that natural killer T (NKT) cells can acquire the ability to convert immunosuppressive MDSCs into immunity-promoting antigen-presenting cells. Here we will review the cross-talk between MDSCs and other immune cells, focusing on Treg cells and NKT cells. We will consider its impact on basic and applied cancer research and discuss how targeting MDSCs may pave the way for future immunocombination therapies.read more
Citations
More filters
Journal ArticleDOI
Microenvironmental regulation of tumor progression and metastasis.
TL;DR: The paradoxical roles of the tumor microenvironment during specific stages of cancer progression and metastasis are discussed, as well as recent therapeutic attempts to re-educate stromal cells within the TME to have anti-tumorigenic effects.
Journal Article
Identification of discrete tumor-induced myeloid-derived suppressor cell subpopulations with distinct T-CELL suppressive activity
Kiavash Movahedi,Martin Guiliams,Jan Van den Bossche,Rafael Van den Bergh,Conny Gysemans,Alain Beschin,Patrick De Baetselier,Jo A. Van Ginderachter +7 more
TL;DR: This work identified 2 distinct MDSC subfractions with clear morphologic, molecular, and functional differences, and refined tumor-induced MDSCs functions by uncovering mechanistically distinct M DSC subpopulations, potentially relevant for MDSc-targeted therapies.
Journal ArticleDOI
Myeloid-derived suppressor cells in the tumor microenvironment: expect the unexpected
TL;DR: The most pertinent and controversial issues of MDSC biology and their role in promoting cancer progression are discussed and how these cells may be used in the clinic, both as prognostic factors and as therapeutic targets are highlighted.
Journal ArticleDOI
Radiotherapy and immunotherapy: a beneficial liaison?
TL;DR: Data that provide new mechanistic explanations for the success or failure of radiotherapy are highlighted, and how the combination of immune-modulation and radiation could tip the balance of the host immune response to promote cure is postulated.
Journal ArticleDOI
Exosomes in tumor microenvironment influence cancer progression and metastasis
Christoph Kahlert,Raghu Kalluri +1 more
TL;DR: Different mechanisms associated with biogenesis, payload, and transport of exosomes are discussed, which may exert an immunosuppressive function as well as trigger an anti-tumor response by presenting tumor antigens to dendritic cells.
References
More filters
Journal ArticleDOI
Hallmarks of cancer: the next generation.
TL;DR: Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer.
Journal ArticleDOI
Improved Survival with Ipilimumab in Patients with Metastatic Melanoma.
F. Stephen Hodi,Steven J. O'Day,David F. McDermott,R. W. Weber,Jeffrey A. Sosman,John B. A. G. Haanen,Rene Gonzalez,Caroline Robert,Dirk Schadendorf,Jessica C. Hassel,Wallace Akerley,Alfons J.M. van den Eertwegh,Jose Lutzky,Paul Lorigan,Julia Vaubel,Gerald P. Linette,David W. Hogg,Christian H. Ottensmeier,Céleste Lebbé,Christian Peschel,Ian Quirt,Joseph I. Clark,Jedd D. Wolchok,Jeffrey S. Weber,Jason Tian,Michael Yellin,Geoffrey M. Nichol,Axel Hoos,Walter J. Urba +28 more
TL;DR: Ipilimumab, with or without a gp100 peptide vaccine, as compared with gp100 alone, improved overall survival in patients with previously treated metastatic melanoma.
Journal ArticleDOI
Safety, activity, and immune correlates of anti-PD-1 antibody in cancer.
Suzanne L. Topalian,F. Stephen Hodi,Julie R. Brahmer,Scott N. Gettinger,David Smith,David F. McDermott,John D. Powderly,Richard D. Carvajal,Jeffrey A. Sosman,Michael B. Atkins,Philip D. Leming,David R. Spigel,Scott J. Antonia,Leora Horn,Charles G. Drake,Drew M. Pardoll,Lieping Chen,William H. Sharfman,Robert A. Anders,Janis M. Taube,Tracee L. McMiller,Haiying Xu,Alan J. Korman,Maria Jure-Kunkel,Shruti Agrawal,Dan McDonald,Georgia Kollia,Ashok Kumar Gupta,Jon M. Wigginton,Mario Sznol +29 more
TL;DR: Anti-PD-1 antibody produced objective responses in approximately one in four to one in five patients with non-small-cell lung cancer, melanoma, or renal-cell cancer; the adverse-event profile does not appear to preclude its use.
Journal ArticleDOI
Safety and Activity of Anti–PD-L1 Antibody in Patients with Advanced Cancer
Julie R. Brahmer,Scott S. Tykodi,Scott S. Tykodi,Laura Q.M. Chow,Wen-Jen Hwu,Suzanne L. Topalian,Patrick Hwu,Charles G. Drake,Luis H. Camacho,John S. Kauh,Kunle Odunsi,Henry C. Pitot,Omid Hamid,Shailender Bhatia,Renato G. Martins,Keith D. Eaton,Shuming Chen,Theresa M. Salay,Suresh Alaparthy,Joseph F. Grosso,Alan J. Korman,Susan M. Parker,Shruti Agrawal,Stacie M. Goldberg,Drew M. Pardoll,Ashok Kumar Gupta,Jon M. Wigginton +26 more
TL;DR: Antibody-mediated blockade of PD-L1 induced durable tumor regression and prolonged stabilization of disease in patients with advanced cancers, including non-small-cell lung cancer, melanoma, and renal-cell cancer.
Journal ArticleDOI
Myeloid-derived suppressor cells as regulators of the immune system.
TL;DR: The origin, mechanisms of expansion and suppressive functions of MDSCs, as well as the potential to target these cells for therapeutic benefit are discussed.
Related Papers (5)
Myeloid-derived suppressor cells as regulators of the immune system.
Improved Survival with Ipilimumab in Patients with Metastatic Melanoma.
F. Stephen Hodi,Steven J. O'Day,David F. McDermott,R. W. Weber,Jeffrey A. Sosman,John B. A. G. Haanen,Rene Gonzalez,Caroline Robert,Dirk Schadendorf,Jessica C. Hassel,Wallace Akerley,Alfons J.M. van den Eertwegh,Jose Lutzky,Paul Lorigan,Julia Vaubel,Gerald P. Linette,David W. Hogg,Christian H. Ottensmeier,Céleste Lebbé,Christian Peschel,Ian Quirt,Joseph I. Clark,Jedd D. Wolchok,Jeffrey S. Weber,Jason Tian,Michael Yellin,Geoffrey M. Nichol,Axel Hoos,Walter J. Urba +28 more